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RSC Advances Nov 2021Anthraquinones are privileged chemical scaffolds that have been used for centuries in various therapeutic applications. The anthraquinone moiety forms the core of... (Review)
Review
Anthraquinones are privileged chemical scaffolds that have been used for centuries in various therapeutic applications. The anthraquinone moiety forms the core of various anticancer agents. However, the emergence of drug-resistant cancers warrants the development of new anticancer agents. The research endeavours towards new anthraquinone-based compounds are increasing rapidly in recent years. They are used as a core chemical template to achieve structural modifications, resulting in the development of new anthraquinone-based compounds as promising anticancer agents. Mechanistically, most of the anthraquinone-based compounds inhibit cancer progression by targeting essential cellular proteins. Herein, we review new anthraquinone analogues that have been developed in recent years as anticancer agents. This includes a systematic review of the recent literature (2005-2021) on anthraquinone-based compounds in cell-based models and key target proteins such as kinases, topoisomerases, telomerases, matrix metalloproteinases and G-quadruplexes involved in the viability of cancer cells. In addition to this, the developments in PEG-based delivery of anthraquinones and the toxicity aspects of anthraquinone derivatives are also discussed. The review dispenses a compact background knowledge to understanding anthraquinones for future research on the expansion of anticancer therapeutics.
PubMed: 35492773
DOI: 10.1039/d1ra05686g -
Arquivos Brasileiros de Oftalmologia 2022
Response to: topical cyclosporine A 0.05% before and after surgery to prevent pterygium recurrenceResponse to: topical cyclosporine A 0.05% before and after surgery to prevent pterygium recurrencePterygium: an update on pathophysiology, clinical features, and managementIn vitro study of...
PubMed: 35416901
DOI: 10.5935/0004-2749.20220092 -
International Journal of Environmental... Mar 2022Purpose: To explore whether baseline matrix metalloproteinase (MMP)-8 level in gingival crevicular fluid (GCF) (exposure) can predict the outcome (reduction in probing... (Review)
Review
Purpose: To explore whether baseline matrix metalloproteinase (MMP)-8 level in gingival crevicular fluid (GCF) (exposure) can predict the outcome (reduction in probing pocket depth (PPD) (outcome)) of nonsurgical periodontal therapy (NSPT) (manual or ultrasonic or both) in patients with periodontitis (population/problem) after 3 months. Methods: Six databases (PubMed, Cochrane library, ProQuest, Ovid, Scopus, EBSCO) were searched for relevant articles published until 30 July 2021. Retrieved articles were passed through a three-phase filtration process on the basis of the eligibility criteria. The primary outcome was the change in PPD after 3 months. Quality of the selected articles was assessed using Cochrane Risk of Bias tool (RoB2) and Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tools. Results: From 1306 articles, five were selected for analysis. The results showed high variations in the level of GCF MMP-8 level at baseline. The average amount of reduction in PPD was 1.20 and 2.30 mm for pockets with initial depth of 4−6 mm and >6 mm, respectively. Conclusion: On the basis of available evidence, it was not possible to reach a consensus on the ability of baseline GCF MMP-8 to forecast the outcome of NSPT. This could have been due to variation in clinical and laboratory techniques used. However, consistency in mean PPD reduction after 3 months was shown.
Topics: Gingival Crevicular Fluid; Humans; Matrix Metalloproteinase 8; Periodontitis
PubMed: 35270821
DOI: 10.3390/ijerph19053131 -
Frontiers in Endocrinology 2022The aim of this review is to assess the current evidence regarding the impact of relaxin on incidence of soft tissue hip injuries in women.
PURPOSE
The aim of this review is to assess the current evidence regarding the impact of relaxin on incidence of soft tissue hip injuries in women.
METHODS
A trained research librarian assisted with searches of PubMed, Embase, CINAHL, and SPORTDiscus, with a preset English language filter. The review was completed per the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis methodology. Included studies required assessment of relaxin effects on musculoskeletal health, pelvic girdle stability, or hip joint structures in human subjects. Letters, texts, and opinion papers were excluded.
RESULTS
Our screen yielded 82 studies. Molecularly, relaxin activates matrix metalloproteinases (MMPs) including collagenases MMP-1/-13 and gelatinases MMP-2/-9 to loosen pelvic ligaments for parturition. However, relaxin receptors have also been detected in female periarticular tissues, such as the anterior cruciate ligament, which tears significantly more often during the menstrual cycle peak of relaxin. Recently, high concentrations of relaxin-activated MMP-9 receptors have been found on the acetabular labrum; their expression upregulated by estrogen.
CONCLUSIONS
Menstrual cycle peaks of relaxin activate MMPs, which locally degrade collagen and gelatine. Women have relaxin receptors in multiple joints including the hip and knee, and increased relaxin correlates with increased musculoskeletal injuries. Relaxin has paracrine effects in the female pelvis on ligaments adjacent to hip structures, such as acetabular labral cells which express high levels of relaxin-targeted MMPs. Therefore, it is imperative to investigate the effect of relaxin on the hip to determine if increased levels of relaxin are associated with an increased risk of acetabular labral tears.
Topics: Female; Hip Injuries; Humans; Incidence; Knee Joint; Menstrual Cycle; Relaxin
PubMed: 35185802
DOI: 10.3389/fendo.2022.827512 -
Journal of Periodontal Research Apr 2022One of the most important families of proteases associated with periodontal disease is the family of the matrix metalloproteinases (MMPs). Their activity is regulated by... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
One of the most important families of proteases associated with periodontal disease is the family of the matrix metalloproteinases (MMPs). Their activity is regulated by tissue inhibitors of metalloproteinases (TIMPs), and an imbalance between MMP activity and regulation by TIMPs has been associated with the progression of periodontal disease. This strong interaction between TIMPs and MMPs might be an indication that TIMPs can be used as a biomarker to monitor periodontal disease progression in oral fluids. In particular, TIMP-1 is a frequently studied biomarker for periodontal diseases. Therefore, the aim of this systematic review was to evaluate the scientific literature regarding TIMP-1 concentrations in oral fluids of patients suffering from periodontitis or gingivitis in comparison to healthy individuals.
MATERIAL AND METHODS
PubMed/ MedLine and Web of Science databases were searched electronically. Studies that met the inclusion criteria were systematically evaluated and assessed for eligibility and risk of bias. Meta-analysis was performed through the random effects model to assess the association between periodontitis/gingivitis and TIMP-1 concentration in stimulated saliva, unstimulated saliva, and gingival crevicular fluid (GCF).
RESULTS
The search strategy provided a total of 322 studies of which 10 studies met all inclusion criteria. Two studies investigated TIMP-1 concentrations in GCF, three studies in unstimulated saliva, and five studies investigated TIMP-1 concentrations in stimulated saliva. Three studies revealed that TIMP-1 levels in oral fluids were significantly decreased in periodontal disease. Meta-analysis revealed that there is no statistically significant difference between TIMP-1 concentration in oral fluids of periodontitis/gingivitis patients in comparison to healthy individuals.
CONCLUSIONS
This systematic review with meta-analysis shows that periodontal diseases are not associated with a statistically significant change in TIMP-1 concentration in oral fluids.
Topics: Biomarkers; Gingival Crevicular Fluid; Gingivitis; Humans; Matrix Metalloproteinase 8; Periodontal Diseases; Tissue Inhibitor of Metalloproteinase-1
PubMed: 34850390
DOI: 10.1111/jre.12957 -
The Saudi Dental Journal Nov 2021Oral submucous fibrosis (OSMF) is one of the common oral potentially malignant disorders that can result in severe morbidity. Depending upon the stage of disease,... (Review)
Review
BACKGROUND
Oral submucous fibrosis (OSMF) is one of the common oral potentially malignant disorders that can result in severe morbidity. Depending upon the stage of disease, multiple management therapies exist which include medicinal and surgical approaches. Although the surgical approach is preferred in severe conditions, numerous studies have reported its post-surgical deteriorating outcomes including increased fibrotic changes. To reduce these post-surgical complications, Light amplification by stimulated emission of radiation (Laser) has been introduced and studied as a non-invasive technique to treat oral submucous fibrosis. However, there exists a lack of knowledge about 'which laser shows a better post-treatment outcome'. Accordingly, this review aims to answer this question.
MATERIALS AND METHODS
A systematic review of the published literature was performed using an electronic search in PubMed/Medline, Science Direct, Web of Science, Embase, J- STAGE, Google Scholar, and Scopus databases, from 1952 till 2019 using keywords like, 'Oral submucous fibrosis', 'Treatment', 'Laser', 'Trismus', ' Fibrosis', 'Surgical', 'Non-invasive', and 'Postoperative results'.
RESULTS
The search strategy revealed 20 relevant published studies in which laser had been used to treat 250 patients of OSMF. Effective results were found without any complications in all the cases after follow up.
CONCLUSION
Observing the current literature, it can be concluded that laser might be used as a potential non-invasive approach in the management of OSMF, however, large scale studies are required to investigate the efficacy and other effects of this technology
PubMed: 34803281
DOI: 10.1016/j.sdentj.2020.11.005 -
World Neurosurgery Jan 2022The mechanisms of brain arteriovenous malformation (bAVM) development, formation, and progress are still poorly understood. By gaining more knowledge about the molecular...
BACKGROUND
The mechanisms of brain arteriovenous malformation (bAVM) development, formation, and progress are still poorly understood. By gaining more knowledge about the molecular signature of bAVM in relation to hemorrhage, we might be able to find biomarkers associated with this serious complication, which can function as a goal for further research and can be a potential target for gene therapy.
AIMS
To provide a comprehensive overview of the molecular signature of bAVM-related hemorrhage We conducted a systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, of articles published in Embase, Medline, Cochrane central, Scopus, and Chinese databases (CNKI, Wanfang).
SUMMARY OF REVIEW
Our search identified 3944 articles, of which 3108 remained after removal of duplicates. After title, abstract, and full-text screening, 31 articles were included for analysis. The results show an overview of molecular characteristics. Several genetic polymorphisms are identified that increase the risk of bAVM rupture by increasing the expression of certain inflammatory cytokines (interleukin [IL]-6, IL-17A, IL-1β, and tumor necrosis factor-α), NOTCH pathways, matrix metalloproteinase-9, and vascular endothelial growth factor-α.
CONCLUSIONS
Several molecular factors are associated with the risk of bAVM-related hemorrhage. These factors are associated with increased inflammation on the cellular level and changes in the endothelium leading to instability of the vessel wall. Further investigation of these biomarkers regarding hemorrhage rates, together with their relationship with noninvasive diagnostic methods, should be a goal of future studies to improve the patient specific risk estimation and future treatment options.
Topics: Arteriovenous Fistula; Cerebral Hemorrhage; Humans; Intracranial Arteriovenous Malformations; Polymorphism, Genetic
PubMed: 34687935
DOI: 10.1016/j.wneu.2021.10.114 -
Progress in Orthodontics Oct 2021MicroRNAs (miRNAs) are non-coding short, single-stranded RNA molecules that may serve as biomarkers for various inflammatory and molecular mechanisms underlying bone and... (Review)
Review
BACKGROUND
MicroRNAs (miRNAs) are non-coding short, single-stranded RNA molecules that may serve as biomarkers for various inflammatory and molecular mechanisms underlying bone and tissue remodeling consequent to orthodontic force application.
METHODS
A thorough literature search in major databases was conducted in March 2021 to generate evidence for miRNAs in orthodontics, with prior PROSPERO registration. The initial search revealed 920 articles, subjected to strict selection criteria according to PRISMA, and resulted in final inclusion of four studies. Quality assessment by QUADAS-2 classified three studies as unclear risk-of-bias while the applicability was high. Further, bioinformatic analysis was performed to identify the target genes from the miRNA database (miRDB) and TargetScan databases and their protein-protein interaction pathways with the STRING analysis.
RESULTS
Multiple miRNAs in gingival crevicular fluid (GCF) of orthodontic patients were seen, including miRNA-21, 27(a/b), 29(a/b/c), 34,146(a/b), 101, and 214 along with matrix metalloproteinases (MMPs)-1, 2, 3, 8, 9, 14 in one study. A statistically significant increase in expression of miRNA-29a/b/c,101, 21 from pre-treatment (before initiation of retraction) was seen to reach a peak at 4-6 weeks (wk) of retraction. On the contrary, miRNA-34a showed downregulation from the 1 day to 4 wk of retraction and also, negatively correlated with MMPs-2,9,14 levels at the same observation times. The distance of canine movement showed mild correlation with miRNA-27a/b, 214 at 2 wk of retraction. Bioinformatics revealed 1213 mutual target genes which were analyzed for inter-relational pathways using Cytoscape plugin, MCODE. Further, 894 prominent protein interactions were identified from the STRING database and SMAD4, IGF1, ADAMTS6, COL4A1, COL1A1, COL3A1, FGFR1, COL19A1, FBN1, COL5A1, MGAT4A, LTBP1, MSR1, COL11A1, and COL5A3 were recognized as the hub genes. Their interactions were able to isolate multiple miRNAs: hsa-miR-34a-5p, hsa-miR-29b-2-5p, hsa-miR-29b-3p, hsa-miR-34a-3p, hsa-miR-27a-5p, hsa-miR-29a-5p, hsa-miR-29b-1-5p, hsa-miR-29c-3p, hsa-miR-214-5p, hsa-miR-27a-3p, hsa-miR-29a-3p, hsamiR-146-5p, which were found promising as biomarkers for tooth movement.
CONCLUSIONS
Our results support using miRNAs as biomarkers in varied orthodontic study designs and for inter-relationships with pathological settings like periodontal disease, pre-malignancies, or conditions like obesity or metabolic irregularities, etc. The identified target genes and their protein interaction pathways can be used to propose precision therapies, focusing on ideal tooth movement with minimal iatrogenic side-effects.
Topics: ADAMTS Proteins; Biomarkers; Computational Biology; Gingival Crevicular Fluid; Humans; MicroRNAs; Orthodontics; Saliva
PubMed: 34632546
DOI: 10.1186/s40510-021-00377-1 -
The European Respiratory Journal Apr 2022Blood-derived biomarkers have been described extensively as potential prognostic markers in idiopathic pulmonary fibrosis (IPF), but studies have been limited by... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Blood-derived biomarkers have been described extensively as potential prognostic markers in idiopathic pulmonary fibrosis (IPF), but studies have been limited by analyses using data-dependent thresholds, inconsistent adjustment for confounders and an array of end-points, thus often yielding ungeneralisable results. Meta-analysis of individual participant data (IPD) is a powerful tool to overcome these limitations. Through systematic review of blood-derived biomarkers, sufficient studies with measurements of matrix metalloproteinase (MMP)-7 were identified to facilitate standardised analyses of the prognostic potential of this biomarker in IPF.
METHODS
Electronic databases were searched on 12 November 2020 to identify prospective studies reporting outcomes in patients with untreated IPF, stratified according to at least one pre-specified biomarker, measured at either baseline, or change over 3 months. IPD were sought for studies investigating MMP-7 as a prognostic factor. The primary outcome was overall mortality according to standardised MMP-7 z-scores, with a secondary outcome of disease progression in 12 months, all adjusted for age, gender, smoking and baseline forced vital capacity.
RESULTS
IPD was available for nine studies out of 12 identified, reporting outcomes from 1664 participants. Baseline MMP-7 levels were associated with increased mortality risk (adjusted hazard ratio 1.23, 95% CI 1.03-1.48; I=64.3%) and disease progression (adjusted OR 1.27, 95% CI 1.11-1.46; I=5.9%). In limited studies, 3-month change in MMP-7 was not associated with outcomes.
CONCLUSION
IPD meta-analysis demonstrated that greater baseline MMP-7 levels were independently associated with an increased risk of poor outcomes in patients with untreated IPF, while short-term changes did not reflect disease progression.
Topics: Biomarkers; Disease Progression; Humans; Idiopathic Pulmonary Fibrosis; Matrix Metalloproteinase 7; Prospective Studies
PubMed: 34588192
DOI: 10.1183/13993003.01612-2021 -
Biomolecules Aug 2021Metalloproteinases (MMPs) have an important role in tissue remodeling and have been shown to have an effect on tumor progression, invasion, metastasis formation, and...
Metalloproteinases (MMPs) have an important role in tissue remodeling and have been shown to have an effect on tumor progression, invasion, metastasis formation, and apoptosis in several tumors, including mesothelioma. Mesothelioma is a rare tumor arising from pleura and peritoneum and is frequently associated with asbestos exposure. We have performed a systematic search of PubMed.gov and ClinicalTrials.gov databases to retrieve and review three groups of studies: studies of MMPs expression in tumor tissue or body fluids in patients with mesothelioma, studies of MMPs genetic variability, and studies of MMPs as potential novel drug targets in mesothelioma. Several studies of MMPs in mesothelioma tissues reported a link between higher expression levels of commonly studied MMPs and clinical parameters, such as overall survival. Fewer studies have investigated genetic variability of genes. Nevertheless, these studies suggested that certain genetic variants in genes can have either protective or tumor-promoting effects on mesothelioma patients. MMPs have been also reported as novel drug targets, but so far no clinical trials of MMP inhibitors are registered in mesothelioma. In conclusion, MMPs play an important role in mesothelioma, but further studies are needed to elucidate the potentials of MMPs as biomarkers and drug targets in mesothelioma.
Topics: Biomarkers, Tumor; Body Fluids; Genetic Variation; Humans; Matrix Metalloproteinases; Mesothelioma; Molecular Targeted Therapy
PubMed: 34572485
DOI: 10.3390/biom11091272