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Biomolecules Jan 2024Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of... (Review)
Review
Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of this review are to analyze a specific family of MPs, the matrix metalloproteinases (MMPs), in the most common chronic and complex diseases that affect patients' social lives and to better understand the nature of the associations between MMPs and the psychosocial environment. In accordance with the PRISMA extension for a scoping review, an examination was carried out. A collection of 24 studies was analyzed, focusing on the molecular mechanisms of MMP and their connection to the manifestation of social aspects in human disease. The complexity of the relationship between MMP and social problems is presented via an interdisciplinary approach based on complexity paradigm as a new approach for conceptualizing knowledge in health research. Finally, two implications emerge from the study: first, the psychosocial states of individuals have a profound impact on their overall health and disease conditions, which implies the importance of adopting a holistic perspective on human well-being, encompassing both physical and psychosocial aspects. Second, the use of MPs as biomarkers may provide physicians with valuable tools for a better understanding of disease when used in conjunction with "sociomarkers" to develop mathematical predictive models.
Topics: Humans; Biomarkers; Proteolysis; Physicians; Zinc; Matrix Metalloproteinases
PubMed: 38254696
DOI: 10.3390/biom14010096 -
European Review For Medical and... May 2024Periimplantitis (PI) is a complex multifactorial chronic disease caused by interactions between bacteria, host immune-inflammatory responses, and genetic or... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Periimplantitis (PI) is a complex multifactorial chronic disease caused by interactions between bacteria, host immune-inflammatory responses, and genetic or environmental factors that modify buccal eutrophism. In daily clinical practice, an increase in the prevalence of PI (8%) determined the need to establish the PI causes and set optimal therapeutic strategies. The interleukin family (IL-1), a group of cytokines, triggers and perpetuates peri-implantitis. Therefore, they could be used as biomarkers for diagnosis and treatment. This systematic review aimed to analyze the correlation between IL-1 allelic polymorphism (IL-1A -889, IL-1β -511, IL-1β +3954) and the PI disease.
MATERIALS AND METHODS
Selected databases were PubMed, Scopus, and Cochrane Library. The search strategy included the following terms: "dental implants"; "periimplantitis"; "interleukin-IL-1"; "polymorphism"; "perimplant bone loss". Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A meta-analysis was conducted on five of 40 review articles. p-values, confidence intervals (CI), and Odds ratios (OR) were assessed. In 4 articles, the p-value was lower than 0.05, confirming the statistical significance of the result.
RESULTS
The prevalence of the selected studies reported the existence of a causal association between polymorphisms of IL-1 and the onset of peri-implantitis, especially for IL-1 allelic variants associated with further polymorphic genes encoding for IL-6, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMP)-8, IL-1Na, IL-8, IL-18, osteopontin (OPN). In addition, the presence of the IL-1 polymorphism and PI is particularly higher in smokers, diabetes, and autoimmune disease patients.
CONCLUSIONS
The detection of salivary biomarkers is, therefore, a diagnostic tool with a high potential to intercept the PI early and act with appropriate and non-invasive treatment. Due to the continued technological innovation in biomarkers and diagnostic sciences, further studies are needed to investigate the role of these biochemical mediators. The results of studies and the recent technological innovation in biomarkers and diagnostic sciences will allow further research to investigate the role of these biochemical mediators.
Topics: Humans; Peri-Implantitis; Polymorphism, Genetic; Interleukin-1; Dental Implants
PubMed: 38856132
DOI: 10.26355/eurrev_202405_36293 -
PeerJ 2024To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment.
METHODOLOGY
PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias.
RESULTS
Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor- (PDGFR-) ( = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) ( < 0.0001), matrix metalloproteinase (MMP) 9 ( < 0.0001), MMP 11 ( < 0.0001) and MMP 13 ( = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of -smooth muscle actin (-SMA) ( = 0.0002), podoplanin (PDPN) ( = 0.0008), and PDGFR- ( = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR- expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2).
CONCLUSIONS
The high expression of -SMA, PDPN, PDGFR- in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.
Topics: Humans; Female; Breast Neoplasms; Cancer-Associated Fibroblasts; Tissue Inhibitor of Metalloproteinase-2; Biomarkers, Tumor; Breast; Receptor, Platelet-Derived Growth Factor beta
PubMed: 38410801
DOI: 10.7717/peerj.16958 -
BMJ Open Oct 2023Very few studies and limited information are available regarding the mechanism of fibrosis in tuberculosis (TB). This study aimed to identify, describe and synthesise... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Very few studies and limited information are available regarding the mechanism of fibrosis in tuberculosis (TB). This study aimed to identify, describe and synthesise potential biomarkers of the development of tissue fibrosis induced by TB through a systematic method and meta-analysis.
METHODS
A literature search was performed using keywords according to the topic from electronic databases (ScienceDirect and PubMed) and other methods (websites, organisations and citations). Studies that matched predetermined eligibility criteria were included. The quality assessment tool used was the Quality Assessment of Diagnostic Accuracy Score 2, and the data obtained were processed using Review Manager V.5.3.
RESULTS
Of the 305 studies, 7 met the eligibility criteria with a total sample of 365. The results of the meta-analysis showed that the post-TB group of patients with pulmonary parenchymal fibrosis had a higher transforming growth factor (TGF)-β level (6.09) than the control group (1.82), with a 4.27 (95% CI: 0.92 to 7.61) mean difference. Moreover, patients with residual pleural thickening post-TB had a higher mean of TGF-β (0.61) than the control group (0.56), with a 0.05 (95% CI: 0.04 to 0.06) mean difference. Besides TGF-β, our qualitative synthesis also found that matrix metalloproteinase-1 might have a role in forming and developing pulmonary tissue fibrosis, thus, could be used as a predictor marker in the formation of fibrotic lesions in patients with TB. In addition, several other biomarkers were assessed in the included studies, such as tumour necrosis factor-α, interleukin (IL)-4, IL-8, IL-10, plasminogen activator inhibitor-1 and platelet-derived growth factor. However, this study is not intended to examine these biomarkers.
CONCLUSIONS
There were differences in the results of TGF-β levels in patients with fibrotic lesions compared with controls. TGF-β might be a biomarker of fibrotic tissue formation or increased pulmonary tissue fibrosis in post-TB patients. However, further studies are needed on a larger scale.
Topics: Humans; Transforming Growth Factor beta; Tuberculosis; Fibrosis; Pulmonary Fibrosis; Biomarkers; Matrix Metalloproteinases; Transforming Growth Factors
PubMed: 37827747
DOI: 10.1136/bmjopen-2022-070377 -
Gland Surgery Jan 2024Radiofrequency ablation (RFA) utilizes minimally invasive high-energy current to precisely ablate tumor cells. It has been utilized in many cancer types including...
BACKGROUND
Radiofrequency ablation (RFA) utilizes minimally invasive high-energy current to precisely ablate tumor cells. It has been utilized in many cancer types including thyroid, lung, and liver cancer. It has been shown to provide adequate ablative margins with minimal complications; however, incomplete RFA may lead to recurrence of tumor. The underlying cellular mechanism and behavior of ablated cancer tissue is poorly understood.
METHODS
A systematic review was performed, searching EMBASE, Web of Science, PubMed, and Scopus for studies published up to March 2022 and reported following PRISMA guidelines. Collection was performed by two groups of investigators to avoid risk of bias. The Cochrane Collaboration's tool was used for assessing risk of bias. We identified human, , and research studies utilizing RFA for tumor tissues. We required that the studies included at least one of the following: complications, recurrence, or survival, and took interest to studies identifying cellular signaling pathway patterns after RFA. Descriptive statistical analysis was performed in 'R' software including mean and confidence interval.
RESULTS
The most frequent cancers studied were liver and lung cancers accounting for 57.4% (N=995) and 15.4% (N=267), followed by esophageal (N=190) and breast cancer (N=134). The most common reported complications were bleeding (19%) and post-operative pain (14%). In our literature search, four independent studies showed upregulation and activation of the VEGF pathway following RFA, four showed upregulation and activation of the AKT pathway following RFA, three studies demonstrated involvement of matrix metalloproteinases, and four showed upregulation of c-Met protein following RFA.
CONCLUSIONS
In our review and meta-analysis, we identify several proteins and pathways of interest of which are important in wound healing, angiogenesis, and cellular growth and survival. These proteins and pathways of interest may implicate areas of research towards RFA resistance and cancer recurrence.
PubMed: 38323236
DOI: 10.21037/gs-22-555 -
Connective Tissue Research Mar 2024The aim of this study was to comprehensively examine and summarize the available in vitro evidence regarding the relationship between mechanical stimulation and... (Review)
Review
OBJECTIVE
The aim of this study was to comprehensively examine and summarize the available in vitro evidence regarding the relationship between mechanical stimulation and biomarkers of collagen synthesis in human-derived tendon cells.
METHODS
Systematic review with narrative analyses and risk of bias assessment guided by the Health Assessment and Translation tool. The electronic databases MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid) and COMPENDEX (Engineering Village) were systematically searched from inception to 3 August 2023. Inclusion criteria encompassed English language, original experimental, or quasi-experimental in vitro publications that subjected human tendon cells to mechanical stimulation, with collagen synthesis (total collagen, type I, III, V, XI, XII, and XIV) and related biomarkers (matrix metalloproteinases, transforming growth factor β, scleraxis, basic fibroblast growth factor) as outcomes.
RESULTS
Twenty-one publications were included. A pervasive definite high risk of bias was evident in all included studies. Owing to incomplete outcome reporting and heterogeneity in mechanical stimulation protocols, planned meta-analyses were unfeasible. Reviewed data suggested that human tendon cells respond to mechanical stimulation with increased synthesis of collagen (e.g., COL1A1, procollagen, total soluble collagen, etc.), scleraxis and several matrix metalloproteinases. Results also indicate that mechanical stimulation dose magnitude may influence synthesis in several biomarkers.
CONCLUSIONS
A limited number of studies, unfortunately characterized by a definite high risk of bias, suggest that in vitro mechanical stimulation primarily increases type I collagen synthesis by human tendon cells. Findings from this systematic review provide researchers and clinicians with biological evidence concerning the possible beneficial influence of exercise and loading on cellular-level tendon adaptation.
Topics: Humans; Collagen; Tendons; Collagen Type I; Biomarkers; Matrix Metalloproteinases
PubMed: 38375562
DOI: 10.1080/03008207.2024.2313582 -
Frontiers in Cellular and Infection... 2023The presence of host collagenases in the degradation of the protein matrix at later stages of carious dentin lesions development, as well as the potential involvement of... (Review)
Review
INTRODUCTION AND AIM
The presence of host collagenases in the degradation of the protein matrix at later stages of carious dentin lesions development, as well as the potential involvement of bacterial collagenases, have been suggested but lack conclusive evidence. This study aims to conduct a systematic review to comprehensively assess the profile of host and bacterial-derived collagenolytic proteases in both root and coronal dentin carious lesions.
METHODS
The search was performed in eight databases and the grey literature. Studies evaluating dentin, extracted teeth, or biofilms from natural caries lesions were included. The methodological quality of studies was assessed using the Joanna Briggs Institute tool. Synthesis of the results and the certainty of evidence were performed following the Synthesis without Meta-analysis (SWiM) checklist and GRADE approach for narrative synthesis, respectively.
RESULTS
From 935 recovered articles, 18 were included. Although the evidence was very uncertain, it was possible to suggest that 1) MMP-2, MMP-9, MMP-13, and CT-B may be increased in carious dentin when compared to sound dentin; 2) there is no difference in MMP-2 presence, while MMP-13 may be increased in root when compared to coronal carious dentin; 3) there is no difference of MMP-2 and MMP-9 expression/activity before and after cavity sealing; 4) MMP-8 may be increased in the dentin before cavity sealing compared to dentin after cavity sealing; 5) there is no difference of MMP-20 in irradiated vs. non-irradiated carious dentin. MMP-20 probably reduces in carious outer dentin when compared to carious inner dentin (moderate certainty). Genes encoding bacterial collagenolytic proteases and protein-degrading bacteria were detected in coronal and root carious lesions.
CONCLUSION
Trends in the direction of the effect were observed for some collagenolytic proteases in carious dentin, which may represent a potential target for the development of new treatments. (Protocol register-PROSPERO: CRD42020213141).
Topics: Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Dentin; Matrix Metalloproteinase 13; Peptide Hydrolases; Matrix Metalloproteinase 20; Collagenases; Bacteria; Dental Caries
PubMed: 38029242
DOI: 10.3389/fcimb.2023.1278754 -
Experimental and Therapeutic Medicine Jun 2024The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear. It has been found that interleukin-6 (IL-6) rs1800795 locus and matrix metalloproteinase-3...
The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear. It has been found that interleukin-6 (IL-6) rs1800795 locus and matrix metalloproteinase-3 (MMP-3) rs3025058 locus gene polymorphisms may be associated with AIS susceptibility, which has been controversial and needs to be further confirmed by updated meta-analysis. The aim of the present study was to investigate the association of MMP-3 rs3025058 and IL-6 rs1800795 single nucleotide polymorphisms (SNPs) with susceptibility to AIS. All relevant articles that met the criteria were retrieved and included, and the publication dates were limited from January 2005 to December 2023. The allele frequencies and different genotype frequencies of IL-6 rs1800795 and MMP-3 rs3025058 loci in each study were extracted and statistically analyzed by ReviewManager 5.4 software, and the odds ratio (OR) and 95% confidence interval (95% CI) of different genetic models were calculated. The results of the meta-analysis showed that there was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS. The allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility (5A vs. 6A, OR=1.18; 95% CI, 1.04-1.33; 5A5A vs. 6A6A, OR=1.65; 95% CI, 1.23-2.21; and 5A5A vs. 5A6A + 6A6A, OR=1.54; 95% CI, 1.19-1.99). Results of subgroup analysis revealed that the allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility in the Caucasian population, and the susceptibility of AIS was associated with the genotype 5A5A of MMP-3 rs3025058 SNP in an Asian population. There was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS, while the allele 5A of MMP-3 rs3025058 locus was associated with the susceptibility to AIS, especially in the Caucasian population.
PubMed: 38756907
DOI: 10.3892/etm.2024.12555 -
Journal of Clinical Periodontology Nov 2023To determine the accuracy of biomarker combinations in gingival crevicular fluid (GCF) and saliva through meta-analysis to diagnose periodontitis in systemically healthy... (Meta-Analysis)
Meta-Analysis Review
AIM
To determine the accuracy of biomarker combinations in gingival crevicular fluid (GCF) and saliva through meta-analysis to diagnose periodontitis in systemically healthy subjects.
METHODS
Studies on combining two or more biomarkers providing a binary classification table, sensitivity/specificity values or group sizes in subjects diagnosed with periodontitis were included. The search was performed in August 2022 through PUBMED, EMBASE, Cochrane, LILACS, SCOPUS and Web of Science. The methodological quality of the articles selected was evaluated using the QUADAS-2 checklist. Hierarchical summary receiver operating characteristic modelling was employed to perform the meta-analyses (CRD42020175021).
RESULTS
Twenty-one combinations in GCF and 47 in saliva were evaluated. Meta-analyses were possible for six salivary combinations (median sensitivity/specificity values): IL-6 with MMP-8 (86.2%/80.5%); IL-1β with IL-6 (83.0%/83.7%); IL-1β with MMP-8 (82.7%/80.8%); MIP-1α with MMP-8 (71.0%/75.6%); IL-1β, IL-6 and MMP-8 (81.8%/84.3%); and IL-1β, IL-6, MIP-1α and MMP-8 (76.6%/79.7%).
CONCLUSIONS
Two-biomarker combinations in oral fluids show high diagnostic accuracy for periodontitis, which is not substantially improved by incorporating more biomarkers. In saliva, the dual combinations of IL-1β, IL-6 and MMP-8 have an excellent ability to detect periodontitis and a good capacity to detect non-periodontitis. Because of the limited number of biomarker combinations evaluated, further research is required to corroborate these observations.
Topics: Humans; Chemokine CCL3; Interleukin-6; Matrix Metalloproteinase 8; Periodontitis; Biomarkers; Interleukin-1beta; Gingival Crevicular Fluid; Saliva
PubMed: 37608638
DOI: 10.1111/jcpe.13854 -
Journal of Affective Disorders Jun 2024Bipolar disorders (BD) are chronic, debilitating disorders. The blood-brain barrier (BBB) has been increasingly investigated in BD. This systematic review aimed to... (Review)
Review
BACKGROUND
Bipolar disorders (BD) are chronic, debilitating disorders. The blood-brain barrier (BBB) has been increasingly investigated in BD. This systematic review aimed to assess the available evidence on the relationship between BD and markers of BBB dysfunction.
METHODS
A systematic search in PubMed, Embase, PsycINFO, CINAHL and Web of Science was run where the primary outcomes were BBB markers such as S100B, albumin ratio, matrix metalloproteinase (MMP), cell adhesion molecule (CAM), and tight junction proteins. Techniques included blood, cerebrospinal fluid (CSF), post-mortem, genetic and imaging methods in BD compared to healthy controls.
RESULTS
55 studies were identified, 38 of which found an association between BD and markers of BBB dysfunction. 16/29 studies found increased blood/CSF albumin ratio, S100B, CAMs or MMP levels in BD participants compared to controls. 5/19 post-mortem studies found increased levels of chondroitin sulphate proteoglycans, intercellular CAM, neurexin or claudin-5 mRNA in distinct locations throughout the brain in BD compared to controls. One imaging study identified extensive BBB leakage in 30 % of BD participants, compared to 0 % in controls.
LIMITATIONS
The diversity in methodologies used in the included studies makes direct comparison of results challenging. Furthermore, imaging methods are the gold standard, but only one study used them. Other markers are only indicative of BBB permeability.
CONCLUSIONS
This review suggests an association between BD and BBB dysfunction. Further research is needed to provide definite answers considering the existing literature's limitations, and to clarify whether this association provides a pathogenic mechanism, or is an epiphenomenon of BD.
PubMed: 38897301
DOI: 10.1016/j.jad.2024.06.032