MMP-9 Concentrations Research Articles

SYNOVIAL FLUID NEUTROPHILS PLAY A ROLE IN THE PATHOPHYSIOLOGY OF KNEE OSTEOARTHRITIS: A PHENOTYPIC AND FUNCTIONAL STUDY

An increased number of neutrophils (NEUs) has long been associated with infections in the knee joints; their contribution to knee osteoarthritis (KOA) pathophysiology remains largely unexplored. This study aimed to compare the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF).Flow cytometric analysis, protein level measurements (ELISA), NEU oxidative burst assays, detection of NEU phagocytosis (pHrodoTM Green Zymosan BiparticlesTM Conjugate for Phagocytosis), morphological analysis of the SF-derived/synovial tissue NEUs, and cultivation of human umbilical vein endothelial cells (HUVECs) using SF supernatant were used to characterise NEUs functionally/morphologically.Results: Compared with INF NEUs, KOA NEUs were characterised by a lower expression of CD11b, CD54 and CD64, a higher expression of CD62L, TLR2 and TLR4, and lower production of inflammatory mediators and proteases, except CCL2.Functionally, KOA NEUs displayed an increased production of radical oxygen species and phagocytic activity compared with INF NEUs. Morphologically, KOA and INF cells displayed different cell sizes and morphology, histological characteristics of the surrounding synovial tissues and influence on endothelial cells. KOA NEUs were further subdivided into two groups: SF containing <10% and SF with 10%–60% of NEUs. Analyses of two KOA NEU subgroups revealed that NEUs with SF <10% were characterised by 1) higher CD54, CD64, TLR2 and TLR4 expression on their surface; 2) higher concentrations of TNF-α, sTREM-1, VILIP-1, IL-1RA and MMP-9 in SFs.Our findings reveal a key role for NEUs in the pathophysiology of KOA, indicating that these cells are morphologically and functionally different from INF NEUs. Further studies should explore the mechanisms that contribute to the increased number of NEUs and their crosstalk with other immune cells in KOA.This study was supported by the Ministry of Health of the Czech Republic (NU20-06-00269; NU21-06-00370).

Abstract 5456: Application of a multiplex urinalysis test for predicting treatment response in patients with BCG unresponsive bladder cancer: a pilot study

Abstract Introduction and Objective: Recently, we reported that OncuriaTM, a multiplex urinalysis test, could be predictive of BCG treatment response. Furthermore, high-grade BCG unresponsive bladder cancer have limited treatment options. Such patients are offered either radical cystectomy or systemic therapy. One of the systemic therapies include immune-oncology agents, e.g., PD-1 or PD-L1 inhibitors. In this study, we tested the performance of OncuriaTM in a BCG unresponsive cohort to determine if it could predict response to a PDL1 inhibitor. Methods: OncuriaTM data was evaluated in voided urine samples obtained from a prospectively collected cohort of 18 subjects who have BCG-unresponsive NMIBC with treatment of atezolizumab monotherapy or atezolizumab BCG combination (provided by Genentech, NCT02792192). The urine samples were collected prior to treatment in both arms. The OncuriaTM test, which measures 10 cancer-associated biomarkers was performed in an independent clinical laboratory. Predictive models were previously developed using supervised learning and cross-validation analyses. Model performance was validated using ROC curves. Results: Pre-treatment urinary concentrations of MMP9, VEGFA, CA9, SDC1, PAI1, APOE, A1AT, ANG and MMP10 were increased in patients who developed disease recurrence. A combinatorial predictive model of treatment outcome achieved sensitivity and specificity of >90%. Conclusion: Previous pilot study found that monitoring the urinary levels of a cancer-associated biomarker panel enabled the discrimination of patients who did not respond to intravesical BCG therapy. In this study, we noted the performance of OncuriaTM for the prediction of systemic PDL1 inhibitor treatment response. A limitation of this study includes its small sample size. With further study, the multiplex OncuriaTM test may be applicable for the clinical evaluation of bladder cancer patients who have not previously responded to intravesical BCG treatment and is considering systemic immune-oncology options. Citation Format: Hideki Furuya, Kaoru Murakami, Ian Pagano, Runpu Chen, Yijun Sun, Nari Kim, Edward E. Kadel, Cheryl V. Wong, Nicole Davarpanah, Charles J. Rosser. Application of a multiplex urinalysis test for predicting treatment response in patients with BCG unresponsive bladder cancer: a pilot study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5456.

PD25-04 APPLICATION OF A MULTIPLEX URINALYSIS TEST FOR PREDICTING TREATMENT RESPONSE IN PATIENTS WITH BCG UNRESPONSIVE BLADDER CANCER: A PILOT STUDY

You have accessJournal of UrologyCME1 Apr 2023PD25-04 APPLICATION OF A MULTIPLEX URINALYSIS TEST FOR PREDICTING TREATMENT RESPONSE IN PATIENTS WITH BCG UNRESPONSIVE BLADDER CANCER: A PILOT STUDY Hideki Furuya, Kaoru Murakami, Ian Pagano, Runpu Chen, Yijun Sun, Nari Kim, Edward Kadel, Cheryl Wong, Nicole Davarpanah, and Charles Rosser Hideki FuruyaHideki Furuya More articles by this author , Kaoru MurakamiKaoru Murakami More articles by this author , Ian PaganoIan Pagano More articles by this author , Runpu ChenRunpu Chen More articles by this author , Yijun SunYijun Sun More articles by this author , Nari KimNari Kim More articles by this author , Edward KadelEdward Kadel More articles by this author , Cheryl WongCheryl Wong More articles by this author , Nicole DavarpanahNicole Davarpanah More articles by this author , and Charles RosserCharles Rosser More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003303.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recently, we reported that OncuriaTM, a multiplex urinalysis test, could be predictive of BCG treatment response. Furthermore, high-grade BCG unresponsive bladder cancer have limited treatment options. Such patients are offered either radical cystectomy or systemic therapy. One of the systemic therapies include immune-oncology agents, e.g., PD-1 or PD-L1 inhibitors. In this study, we tested the performance of OncuriaTM in a BCG unresponsive cohort to determine if it could predict response to a PDL1 inhibitor. METHODS: OncuriaTM data was evaluated in voided urine samples obtained from a prospectively collected cohort of 18 subjects who have BCG-unresponsive NMIBC with treatment of atezolizumab monotherapy or atezolizumab BCG combination (provided by Genentech, NCT02792192). The urine samples were collected prior to treatment in both arms. The OncuriaTM test, which measures 10 cancer-associated biomarkers was performed in an independent clinical laboratory. Predictive models were previously developed using supervised learning and cross-validation analyses. Model performance was validated using ROC curves. RESULTS: Pre-treatment urinary concentrations of MMP9, VEGFA, CA9, SDC1, PAI1, APOE, A1AT, ANG and MMP10 were increased in patients who developed disease recurrence. A combinatorial predictive model of treatment outcome achieved sensitivity and specificity of >90%. CONCLUSIONS: Previous pilot study found that monitoring the urinary levels of a cancer-associated biomarker panel enabled the discrimination of patients who did not respond to intravesical BCG therapy. In this study, we noted the performance of OncuriaTM for the prediction of systemic PDL1 inhibitor treatment response. A limitation of this study includes its small sample size. With further study, the multiplex OncuriaTM test may be applicable for the clinical evaluation of bladder cancer patients who have not previously responded to intravesical BCG treatment and is considering systemic immune-oncology options. Source of Funding: NIH/NCI R21CA263230, NIH/NCI R01CA198887 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e730 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hideki Furuya More articles by this author Kaoru Murakami More articles by this author Ian Pagano More articles by this author Runpu Chen More articles by this author Yijun Sun More articles by this author Nari Kim More articles by this author Edward Kadel More articles by this author Cheryl Wong More articles by this author Nicole Davarpanah More articles by this author Charles Rosser More articles by this author Expand All Advertisement PDF downloadLoading ...

Extracellular matrix collagen biomarker levels in patients who underwent pulmonary endarterectomy.

The role of extracellular matrix collagen biomarkers in chronic thromboembolic pulmonary hypertension (CTEPH) is not well known. Our goal was to investigate the matrix metalloproteinase (MMP)-2 and -9 protein levels in patients with CTETH. This is a prospective, cross-sectional study. Patients with CTETH who underwent pulmonary endarterectomy comprise group 1, and the control group included patients who underwent lung surgery without pulmonary hypertension (group 2) between March 2020 and March 2021. In addition to serum levels of MMP-9, the pulmonary endarterectomy and control pulmonary artery tissue samples were measured by the enzyme-linked immunosorbent assay 4pl, cubic, quadratic and Western blot techniques. Levels of MMP-2, which consist of pro MMP-2/ß-actin and active MMP-2/ß-actin and MMP-9/ß-actin, were measured only in the tissue samples. Forty-eight patients were enrolled consecutively in group 1 (n: 24) and group 2 (n: 24). The serum concentrations of MMP-9 were similar in both groups. Similarly, a comparison of tissue sample levels of pro MMP-2/ß-actin (P = 0.496) and active MMP-2/ß-actin (P = 0.216) showed no significant difference between the groups. The tissue samples from patients with CTETH had significantly lower amounts of MMP-9/ß-actin compared to the control group (P = 0.001). This study indicates that serum levels of extracellular matrix collagen biomarkers were similar in patients with CTETH who were candidates for surgery and in patients who had non-pulmonary hypertension who underwent lung surgery. Differences in levels of MMP-9/ß-actin in tissue samples may play a role in pulmonary vascular remodelling in operable patients.

Changes in the Extracellular Matrix in Endometrial and Cervical Cancer: A Systematic Review

Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.

Functional Peptide-Loaded Gelatin Nanoparticles as Eyedrops for Cornea Neovascularization Treatment.

Corneal neovascularization (NV) is a process of abnormal vessel growth into the transparent cornea from the limbus and can disturb the light passing through the cornea, resulting in vision loss or even blindness. The use of nanomedicine as an effective therapeutic formulation in ophthalmology has led to higher drug bioavailability and a slow drug release rate. In this research, we designed and explored the feasibility of a new nanomedicine, gp91 ds-tat (gp91) peptide-encapsulated gelatin nanoparticles (GNP-gp91), for inhibiting corneal angiogenesis. GNP-gp91 were prepared by a two-step desolvation method. The characterization and cytocompatibility of GNP-gp91 were analyzed. The inhibition effect of GNP-gp91 on HUVEC cell migration and tube formation was observed by an inverted microscope. The drug retention test in mouse cornea was observed by in vivo imaging system, fluorescence microscope, and DAPI/TAMRA staining. Finally, the therapeutic efficacy and evaluation of neovascularization-related factors were conducted through the in vivo corneal NV mice model via topical delivery. The prepared GNP-gp91 had a nano-scale diameter (550.6 nm) with positive charge (21.7 mV) slow-release behavior (25%, 240hr). In vitro test revealed that GNP-gp91 enhanced the inhibition of cell migration and tube formation capacity via higher internalization of HUVEC. Topical administration (eyedrops) of the GNP-gp91 significantly prolongs the retention time (46%, 20 min) in the mouse cornea. In chemically burned corneal neovascularization models, corneal vessel area with a significant reduction in GNP-gp91 group (7.89%) was revealed when compared with PBS (33.99%) and gp91 (19.67%) treated groups via every two days dosing. Moreover, GNP-gp91 significantly reduced the concentration of Nox2, VEGF and MMP9 in NV's cornea. The nanomedicine, GNP-gp91, was successfully synthesized for ophthalmological application. These data suggest that GNP-gp91 contained eyedrops that not only have a longer retention time on the cornea but also can treat mice corneal NV effectively delivered in a low dosing frequency, GNP-gp91 eyedrops provides an alternative strategy for clinical ocular disease treatment in the culture.

Analysis of Selected Salivary Adipokines and Cytokines in Patients with Obesity—A Pilot Study

Obesity is a chronic, progressive and relapsing disease that produces many adverse health, social and economic effects. The aim of the study was to analyse the concentrations of selected proinflammatory parameters in the saliva of obese and normal body weight individuals. The study included 116 people divided into two groups: the study group (n = 75, subjects with obesity) and the control group (n = 41, individuals with normal body weight). Bioelectrical impedance analysis was performed, and saliva samples were collected from all study participants to determine the concentrations of selected proinflammatory adipokines and cytokines. Statistically significantly higher concentrations of MMP-2, MMP-9 and IL-1β were found in the saliva of obese women compared to women with normal body weight. Furthermore, statistically significantly higher concentrations of MMP-9, IL-6 and resistin were observed in the saliva of obese men compared to men with normal body weight. Higher concentrations of selected proinflammatory cytokines and adipokines were found in the saliva of obese individuals compared to individuals with normal body weight. It is likely that higher concentrations of MMP-2, MMP-9 and IL-1β can be detected in the saliva of obese women compared to non-obese women, while higher concentrations of MMP-9, IL-6 and resistin can be found in the saliva of obese men compared to non-obese men, which suggests that further research to confirm our observations and determine the mechanisms of development of metabolic complications associated with obesity depending on gender is needed.

Relationship between circulating senescence-associated secretory phenotype levels and severity of type 2 diabetes-associated periodontitis: A cross-sectional study.

Senescence-associated secretory phenotype (SASP) has recently been found to drive comorbid diabetes and periodontitis by inducing a chronic, low-degree inflammatory state. Here, we sought to explore the relationship between circulating SASP and the severity of type 2 diabetes-associated periodontitis (DP). Eighty patients (middle-aged periodontitis, M-P group; aged periodontitis, A-P group; M-DP group; and A-DP group; n=20) provided gingival epithelium, serum, and periodontal clinical parameters. Circulating levels of 12 DP-related SASP factors were analyzed by immunoassay. Correlation between periodontal clinical parameters and circulating SASP levels was analyzed by Spearman's rank correlation coefficient and back propagation artificial neural network (BPNN). Senescence markers (p16, p21, and HMGB1) in gingiva were determined by immunofluorescence assay. M-DP group had increased serum levels of twelve SASP factors compared with the M-P group (p<0.5). Serum levels of IL-6, IL-4, and RAGE were higher in the A-DP group than the A-P group (p<0.5). The circulating concentrations of certain SASP proteins, including IL-1β, IL-4, MMP-8, OPG, RANKL, and RAGE were correlated with the clinical parameters of DP. BPNN showed that serum SASP levels had considerable predictive value for CAL of DP. Additionally, the DP group had higher expressions of p16, p21, and cytoplasmic-HMGB1 in the gingiva than the P group (p<0.5). Significantly enhanced circulating SASP levels and aggravated periodontal destruction were observed in patients with DP. Importantly, a non-negligible association between serum SASP levels and the severity of DP was found.

Targeting Some Key Metalloproteinases by Nano-Naringenin and Amphora coffeaeformis as a Novel Strategy for Treatment of Osteoarthritis in Rats.

Osteoarthritis (OA) represents the highest degenerative disorder. Because cartilage erosion is a common pathological alteration in OA, targeting some key metalloproteinases such as MMP-3, ADAMTS-5 besides their inhibitor TIMP-3 by natural products, could be an effective strategy to protect against osteoarthritis. Forty female Wister rats were categorized into five equal groups. Control, osteoarthritic (OA) (monosodium iodoacetate (MIA) 2 mg/50 µL saline, single intra-articular injection), OA+ indomethacin (2 mg/kg/daily/orally), OA+ nano-naringenin (25 mg/kg/daily/orally), and OA+ Amphora coffeaeformis (772 mg/kg/daily/orally). Treatments were initiated on the 8th day after osteoarthritis induction and continued for 28 days thereafter. Finally, blood and knee joint samples were collected from all rats for biochemical and histopathological evaluations. The current study showed that MIA induced oxidative stress, which resulted in changes in the inflammatory joint markers associated with increased right knee diameter and higher clinical scores for lameness. Amphora coffeaeformis followed by nano-naringenin exhibited a potential anti-arthritic activity by reducing the concentrations of serum MMP-3, ADAMTS-5, and joint MDA and increasing the levels of serum TIMP-3 and joint GSH, similar to indomethacin. The histopathological results confirmed these outcomes. In conclusion, Amphora coffeaeformis and nano-naringenin can be considered as natural therapeutic agents for osteoarthritis owing to their antioxidant and anti-inflammatory activities.

The association of vitamin D status with oxidative stress biomarkers and matrix metalloproteinases in patients with knee osteoarthritis.

The association of vitamin D status with osteoarthritis (OA) has been demonstrated previously. The current study was performed to examine the association of vitamin D status with oxidative stress markers and matrix metalloproteinases (MMPs) in patients with knee OA. This case-control study was conducted on 124 subjects with mild to moderate knee OA and 65 healthy controls. Demographic data was collected from all participants at baseline. Serum levels of vitamin D as well as markers of oxidative stress including malondialdehyde (MDA), total oxidant status (TOS), superoxide dismutase (SOD), oxidative stress index (OSI), paraoxonase-1 (PON-1), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC) were evaluated for each participant. Furthermore, serum concentrations of MMP-1, MMP-3, MMP-13, and cartilage oligomeric matrix protein (COMP) were measured. The results of the present study indicated that individuals with vitamin D insufficiency had higher levels of MDA, TOS, SOD, and OSI as well as lower levels of PON-1 and TAC. Based on the linear regression analysis, serum vitamin D levels were inversely correlated with MDA, TOS, SOD, OSI, MMP-1, and MMP-13 and positively associated with TAC levels (p < 0.0001). Patients with sufficient vitamin D levels had lower MMP-1 and MMP-13 levels compared to patients with vitamin D insufficiency (p < 0.001 and p < 0.001, respectively). Findings from this study showed a strong association between vitamin D deficiency and increased oxidative stress and MMPs activity in patients with knee OA.

Ex Vivo Analysis of an Association of Mechanical Strength of Dilated Ascending Aorta with Tissue Matrix Metalloproteinases and Cytokines.

We analyzed the associations of the mechanical strength of dilated ascending aorta wall (intraoperative samples from 30 patients with non-syndromic aneurysms) with tissue MMPs and the cytokine system. Some samples were stretched to break on an Instron 3343 testing machine and the tensile strength was calculated; others were homogenized and the concentrations of MMP-1, MMP-2, MMP-7, their inhibitors (TIMP-1 and TIMP-2), and pro- and anti-inflammatory cytokines were determined by ELISA. Direct correlations between aortic tensile strength and concentrations of IL-10 (r=0.46), TNFα (r=0.60), and vessel diameter (r=0.67) and an inverse correlation with patient's age (r=-0.59) were revealed. Compensatory mechanisms supporting the strength of the ascending aortic aneurysm are possible. No associations of MMP-1, MMP-7, TIMP-1, and TIMP-2 with tensile strength and aortic diameter were found.

Decreased ratios of matrix metalloproteinases to tissue-type inhibitors in cerebrospinal fluid in sporadic and hereditary cerebral amyloid angiopathy

BackgroundTo evaluate the potential of cerebrospinal fluid (CSF) levels of matrix metalloproteinases and tissue-type inhibitors (MMP; TIMP), and ratios of MMPs to TIMPs, to function as biomarkers for sporadic or hereditary cerebral amyloid angiopathy (CAA).MethodsCSF concentrations of the matrix metalloproteinases MMP-2, MMP-9 and MMP-14, as well as the tissue inhibitors of metalloproteinases TIMP-1, TIMP-2 and TIMP-3, were determined using immunoassays. These assays were applied to two, independent study groups of sporadic CAA (sCAA) (n = 28/43) and control subjects (n = 40/40), as well as to groups of pre-symptomatic (n = 11) and symptomatic hereditary Dutch-CAA (D-CAA) patients (n = 12), and age-matched controls (n = 22/28, respectively).ResultsIn the sCAA/control cohorts, inconsistent differences were found for individual MMPs and TIMPs, but MMP-2/TIMP-2 (discovery/validation: p = 0.004; p = 0.02) and MMP-14/TIMP-2 ratios (discovery/validation: p < 0.001; p = 0.04) were consistently decreased in sCAA, compared to controls. Moreover, MMP-14 was decreased in symptomatic D-CAA (p = 0.03), compared to controls. The MMP-14/TIMP-1 (p = 0.03) and MMP-14/TIMP-2 (p = 0.04) ratios were decreased in symptomatic D-CAA compared to controls and also compared to pre-symptomatic D-CAA (p = 0.004; p = 0.005, respectively).ConclusionCSF MMP-2/TIMP-2 and MMP-14/TIMP-2 were consistently decreased in sCAA, compared to controls. Additionally, MMP-14/TIMP-2 levels were also decreased in symptomatic D-CAA, compared to both pre-symptomatic D-CAA and controls, and can therefore be considered a biomarker for sporadic and late-stage hereditary forms of CAA.

Prognostic value of interleukin-33, sST2, myeloperoxidase, and matrix metalloproteinase-9 in acute aortic dissection.

Acute aortic dissection (AAD) is a life-threatening cardiovascular emergency. Both neutrophil granzyme and interleukin (IL)-33/ST2 systems have proven to be effective diagnostic markers for AAD. This study aimed to investigate the relationship between plasma IL-33, soluble suppression of tumorigenesis-2 (sST2), myeloperoxidase (MPO), and matrix metalloproteinase (MMP)-9 levels at admission and all-cause mortality in patients with AAD. A total of 155 patients with AAD were enrolled from the Prospective Evaluation of Acute Chest Pain (PEACP) study. Plasma concentrations of IL-33, sST2, and MMP-9 were measured using an enzyme-linked immunosorbent assay, and MPO was detected using a chemiluminescence immunoassay. Aortic anatomical parameters were measured using CT radiography. The primary endpoint was all-cause mortality rate. The median age of the patients was 55 years, and 96 (61.9%) were diagnosed with type A-AAD. After adjusting for confounding factors, the highest tertiles of IL-33, sST2, MPO, and MMP-9 had hazard risks of 0.870 (95% CI: 0.412-1.836, P = 0.714), 3.769 (95% CI: 1.504-9.446, P = 0.005), 4.689 (95% CI: 1.985-11.076, P < 0.001), and 4.748 (95% CI: 1.763-12.784, P = 0.002), respectively, compared to the lowest tertile. Pearson's correlation analysis revealed a significant correlation between these markers (P < 0.001). Moreover, sST2, MPO, and MMP-9 levels had a significant positive correlation with aortic diameter and pseudolumen area (P < 0.001). The biomarkers sST2, MPO, and MMP-9 were independently associated with mortality in patients with AAD. The significant correlation between these biomarkers suggests a pathogenic role for the IL-33/ST2/neutrophil granzyme system in patients with AAD.

Features of the content of matrix metalloproteinases ММР-9 and ММР-2 in mixed saliva of young individuals with dental caries against the background of different level of 25(OH) vitamin D in the body.

The content ofММР-9 and ММР-2 in oral fluid of 105 individuals between the ages of 19 and 23 has been researched.Of these, 42 people are individuals with dental caries and normal level of the active form of vitamin Din serum (25(OH)D >30ng/mL) and 42 people - with 25(OH)D <30 ng/mL level.The control group was composed of 21 individuals with low DMFt index (1,5) and a normal level of 25(OH)D in blood. It has been established that the level of ММР-9 in mixed salivaincreases against the background of dental caries,while the content of ММР-9 and ММР-2 increasessignificantlyamidthe lack and deficiency of25(OH)Din the body. Inverse correlations between the 25(OH)D level in serum and the value ofmatrix metalloproteinasesin saliva have been revealed: noticeable - with the amount of MMP-9 and moderate- with the concentration of MMP-2.

Диагностическое значение биохимических маркеров истмико-цервикальной недостаточности при определении тактики ведения беременных с укороченной шейкой матки

Aim: To determine the value of biochemical markers of isthmic-cervical insufficiency in patients with a shortened cervix for predicting premature birth. Design: А prospective study. Materials and methods. In the second trimester of pregnancy, 100 pregnant women with a high risk of isthmic-cervical insufficiency were examined three times in dynamics (at 12–14, 18–20 and 26–28 weeks). The division into groups was carried out retrospectively taking into account the length of the cervix according to the results of ultrasound cervicometry: Group 1 — 32 patients with a conditionally normal cervical length (26–30 mm), group 2 — 39 patients with a cervical length of 20–25 mm, group 3 — 29 women with a cervical length of less than 20 mm. In each group, the course and outcome of pregnancy were analyzed, and the levels of specific biochemical markers in the blood serum were studied: matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) and serum fibronectin (FN). Results. Concentrations of MMP-2 and MMP-9 are significantly higher in pregnant women of the 2nd and 3rd groups. A significant increase in their levels was noted during the study. The level of serum FN was initially increased in the 2nd and especially in the 3rd group, but decreased during surgical correction. When performing cervicometry, in addition to shortening of the cervix, the most significant ultrasound signs of infection were noted — a sludge phenomenon (accumulation of dense echopositive sediment located near the lower pole of the fetal bladder at the inner throat of the cervix) and suspension in amniotic fluid. Conclusion. Measuring the length of the cervix in combination with the study of the levels of MMP-2, MMP-9 and serum FN, as well as the detection of signs of infection of the urogenital tract will contribute to the timely implementation of preventive measures and a differentiated approach to the choice of tactics for the management of pregnant women with shortening of the cervix. Keywords: shortened cervix, isthmic-cervical insufficiency, collagenogenesis, premature birth, cervicometry.

Quercetin inhibits body weight gain and adipogenesis via matrix metalloproteinases in mice fed a high-fat diet.

Limited studies reported that quercetin inhibited adipogenesis and neovascularization by inhibiting matrix metalloproteinases (MMPs) activity, but such mechanisms have not been elucidated in animal experiments. In this study, we investigated the inhibitory effects of quercetin on weight gain and adipose tissue growth through the regulation of mRNA expressions of adipogenic transcription factors and MMPs in mice fed a high-fat diet (HFD). Five-wk-old C57BL/6J mice were fed a normal diet (ND), HFD, HFD containing 0.05% of quercetin (HFQ0.05), or HFD containing 0.15% of quercetin (HFQ0.15) for 16 wks. Glycerol-3-phosphate dehydrogenase (GPDH) activity was measured using a commercial kit. The mRNA expressions of transcription factors related to adipocyte differentiation were determined by real-time polymerase chain reaction (PCR). The mRNA expressions of MMPs and concentrations of MMPs were measured by real-time PCR and enzyme-linked immunosorbent assay kit, respectively. Quercetin intake reduced body weight gain and epididymal adipose tissue weights (P < 0.05). GPDH activity was higher in the HFD group than in the ND group but lower in the quercetin groups (P < 0.05). The mRNA expressions of CCAAT/enhancer binding protein β (C/EBPβ), C/EBPα, peroxisome proliferator-activated receptor γ, and fatty acid-binding protein 4 were lower in the quercetin groups than in the HFD group (P < 0.05). Similarly, the mRNA expression and concentrations of MMP-2 and MMP-9 were significantly lower in the quercetin groups than in the HFD group (P < 0.05). The study confirms that quercetin suppresses body weight gain and adipogenesis by inhibiting transcription factors related to adipocyte differentiation and MMPs (MMP-2 and MMP-9), in mice fed a HFD.

Effect of Carnosine on the Activity of Matrix Metalloproteinase-2 and Oxidative Stress in the Kidneys in Experimental Urate Nephrolithiasis.

The effect of carnosine on MMP-2 activity and oxidative stress in the kidneys in experimental urate nephrolithiasis was studied. Urate nephrolithiasis was modeled in Wistar rats by intragastric administration of a mixture of oxonic and uric acids. Carnosine was administered intragastrically through a tube in a dose of 15 mg/kg. In rats treated with carnosine, the concentration of MMP-2 in the urine decreased by 3.7 times, and the excretion of MMP-2 with urine decreased by 4.3 times. In the homogenate of the kidneys from rats treated with carnosine, the concentration of TBA-reactive substances decreased by 5 times and the concentration of MMP-2 decreased by 12.7%. After treatment with carnosine, the number of histologically confirmed cases of urate nephrolithiasis decreased by 2 times, while the mean size of urate deposits decreased by 2.7 times. Thus, carnosine inhibits MMP-2 and reduces the intensity of oxidative stress in the kidneys, which prevents the development of urate nephrolithiasis.

Effect of Estradiol on Chondrocytes in the Active Stage of Collagenase- Induced Osteoarthritis

Aims: The aim of the present study is to examine the effect of estradiol on chondrocyte inflammatory potential and apoptosis in a mouse model of osteoarthritis (OA). Background: OA is a degenerative joint disease related to articular cartilage disintegration, together with substantial changes in the subchondral bone. Estradiol (ED) is considered to be an important player in maintaining bone homeostasis. Increasing evidence support the association between the severity of cartilage erosion and chondrocyte death. Objective: It is of great importance to elucidate the role of chondrocytes in the development of OA in relation to estrogen levels. Methods: The present work was conducted on a model of collagenase-induced osteoarthritis (CIOA) in ICR (CD-2) mice. The cytokine and MMP-3 concentrations were assayed by ELISA, and apoptosis of chondrocytes was determined by flow cytometry. Results: ED decreased the number of cultured TGF-β1 positive chondrocytes, reduced the percentage of double-positive CD220+/TNF-α+ chondrocytes. ED reduced the rate of apoptosis and MMP- 13 production of stimulated arthritic chondrocytes, and inhibited the release of inflammatory IL-6 and IL-8 cytokines in vitro. Conclusion: Our results show that ED affects chondrocyte functions as a part of its anti-arthritic mechanism of action and it might be a perspective drug for healing OA.

Evaluation of MMP-9 with atherogenic index and electrocardiogram as a predictor of cardiovascular risk factors in hypertensive patients

Hypertension is the strongest or one of the strongest risk factors for almost all different cardiovascular diseases acquired during life, including coronary disease, left ventricular hypertrophy, and valvular heart diseases. So, the aim of this study was to evaluate the plasma concentration of MMP-9 and AIP in mild to moderate hypertensive patients. : A total of 162 patients with hypertensive case were recruited and compared with the 100 normotensive controls from the Rohilkhand Medical College and Hospital Bareilly. Parameters include waist circumference (WC), Fasting Blood Sugar (FBS), Lipid profile with Atherogenic Index, and Matrix metalloproteinase-2 were estimated in the plasma of all the test groups. Electrocardiography (ECG) was also performed as a cardiovascular tool.There was a significantly increased concentration of WC, FBS, and Lipid parameters except for HDL which is slightly lower in the case group when compared to the control group. The concentration of MMP-9 was also increased, which is positively significant. The mean value of the P-R interval, QRS complex, and QT interval was also increased in hypertensive as compared to the controls.Atherogenic index and MMP-9 are significantly higher in hypertensive patients. So, it could be a biomarker of cardiovascular disease.

Amentoflavone-Enriched Selaginella rossii Protects against Ultraviolet- and Oxidative Stress-Induced Aging in Skin Cells.

Selaginellaceae plants are used in cosmetics to limit skin aging. This study is the first to investigate the anti-aging effects of Selaginella rossii (SR) on ultraviolet B (UVB)- and oxidative stress-induced skin cells. The 95% ethanol extract of Selaginella rossii (SR95E) contained much higher amounts of amentoflavone (AMF), an active compound, than other Selaginellaceae plants and was more effective in inhibiting matrix metalloproteinase (MMP)-1 expression in CCD-986sk fibroblasts. SR95E significantly decreased UVB-induced MMP-1, MMP-2, MMP-3 and MMP-9 expression and enhanced procollagen type I C-peptide content and mRNA expression of collagen type I alpha (COL1A)1 and COL1A2 in CCD-986sk fibroblasts. In HaCaT keratinocytes, SR95E treatment also dose-dependently decreased UVB-induced MMP-1 concentration and MMP-1, MMP-2, MMP-3 and MMP-9 mRNA expression. Moreover, SR95E treatment markedly inhibited UVB-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinase signaling and nuclear factor kappa-B signaling in HaCaT cells. Furthermore, SR95E and AMF markedly regulated the 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced expression of cellular senescence-related markers, including p16, p21 and LMNB1, in HaCaT cells. Overall, this study indicates that SR may have potential as a functional material on preventing UVB- and AAPH-induced skin aging and wrinkles.