MMP-9 Concentrations Research Articles

Immune Profiling of Secreted Factors from Human Vestibular Schwannoma Cells and Tumor-associated Macrophages.

This study compared the immune-related secretory capacity of human vestibular schwannoma (VS) and tumor-assisted macrophages (TAMs) with their normal counterparts (Schwann cells [SC] and peripheral blood monocyte-derived macrophages [Mo-MFs], respectively), and examined relationships with presurgical hearing and tumor size. VS tumors (n = 16), auditory nerve (n = 1), blood (n = 9), and great auricular nerves (n = 3) were used. SCs (S100B+ ) and TAMs (CD68+ ) were isolated from VS tissue for culture. The secreted levels of 65 immune-related factors were measured and compared using unpaired t-tests with Welch correction (schwannoma vs. SCs) or Mann-Whitney tests (TAMs and Mo-MFs). Associations between factor concentration and word recognition (WR), pure-tone average (PTA), and tumor size were evaluated with Spearman correlation. Secreted factors with significantly higher concentrations in schwannoma versus SC supernatants included IL-2 and BAFF, whereas MMP-1, IL-6, FGF-2, VEGF-A, MIP-3α, and GRO-α concentrations were significantly higher in TAMs versus Mo-MFs (all p < 0.05). Worse WR was significantly associated with higher secretion of fractalkine, eotaxin-3, CD30, and IL-16 by VS cells; IP-10, eotaxin-3, multiple interleukins, GM-CSF, SCF, and CD30 by TAMs; and TNF-α and MIP-1α by Mo-MFs (all p < 0.05). Worse PTA was significantly correlated with higher secretion of IL-16 by VS cells (p < 0.05). Larger tumor size was significantly correlated with higher secretion of eotaxin by VS cells, and of IL-7, IL-21, and LIF by TAMs (all p = 0.017). Differential secretion of immune-related factors was observed in schwannoma versus normal SCs and in TAMs versus Mo-MFs, some of which were correlated with worse hearing and larger VS tumors. N/A Laryngoscope, 134:S1-S14, 2024.

Assessment of connective tissue metabolism in patients with head and neck malignancies treated with radiotherapy.

&lt;br&gt;&lt;b&gt;Introduction:&lt;/b&gt; Despite the use of highly specialized irradiation techniques in the treatment of head and neck tumors, it is still impossible to selectively destroy cancer cells without damaging normal structures, including connective tissue cells.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; The aim of the study was to analyze the concentration of degradation markers such as collagen type I (carboxyterminal telopeptide of type I collagen; ICTP) and elastin (elastin-derived peptides; EDPs) as well as selected metalloproteinases (MMP-1, MMP-2, MMP-9) in patients with head and neck malignancies undergoing radiotherapy.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Material and methods:&lt;/b&gt; The test group consisted of 56 men, who underwent radical or palliative radiotherapy. The concentrations of ICTP, EDPs, MMP-1, MMP-2, MMP-9 were determined in three blood samples collected from patients prior to radiotherapy, immediately after its completion and 3 months after the therapy.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Results&lt;/b&gt;: Both radical and palliative radiotherapy contribute to a significant increase in the concentration of EDPs. At the time of healing of post-irradiation lesions, the level of EDPs was reduced in both groups. The ICTP concentration was not affected by radiotherapy. No significant differences were observed in the concentration of MMP-1 and MMP-2 before and after radiotherapy. Radical radiotherapy caused a statistically significant late reduction in the concentration of MMP-9. The lowest concentrations of MMP-1, MMP-2, MMP-9 in the serum of patients qualified for palliative radiotherapy were recorded in a samples collected three months post-irradiation.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The degradation markers of key extracellular matrix structural proteins may be helpful tools in the objective assessment of radiation-induced injuries to the connective tissue.&lt;/br&gt.

Cavin1 activates the Wnt/β-catenin pathway to influence the proliferation and migration of hepatocellular carcinoma

Introduction and ObjectivesCavin1 is a cell membrane caveolin, with controversial function in different tumors. Meanwhile, the role of Cavin1 in hepatocellular carcinoma (HCC) progression remains unclear. In this study, we attempted to elucidate the significance of Cavin1 in HCC occurrence and progression. Materials and MethodsCavin1 content was examined in HCC tissues and paired adjacent normal liver tissues by qRT-PCR and IHC among 81 HCC patients. The Cavin1-mediated regulation of HCC proliferation and metastasis was assessed through in vitro and in vivo experiments. Finally, using GSEA, we found out Cavin1 could be a potential regulator of the Wnt pathway. The alterations of the Wnt pathway-related proteins were identified by Western Blot analysis. ResultsCavin1 was lower expressed in HCC, which implied poor survival outcomes in HCC patients. Phenotypic experiments revealed that Cavin1 strongly suppressed HCC proliferation and migration in vitro and in vivo. Besides, altered epithelial-mesenchymal transition (EMT)-related protein expressions were detected. Based on our GSEA analysis, Cavin1 activated the Wnt pathway, and Western Blot analysis revealed diminished β-catenin, c-Myc, and MMP9 contents upon Cavin1 overexpression. ConclusionsCavin1 suppresses HCC progression by modulating HCC proliferation and migration via inhibiting the Wnt/β-catenin axis activation.

Metalloproteinase-2 in failed back surgery syndrome caused by epidural fibrosis: can it play a role in persistent pain?

Failed Back Surgery Syndrome (FBSS) occurs in 10-40% of patients treated surgically due to disk herniation (DH). There are several factors that can cause a predisposition to FBSS, but the exact pathomechanism has not been elucidated. The aim of this study was to investigate Metalloproteinase-2 (MMP-2) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) activities in a homogeneous group of FBSS patients with epidural fibrosis in comparison to its activity in patients with surgically treated DH. DH, FBSS, and control (CG) groups consisted of 30 subjects. The patients were assessed clinically by the Numerical Rating Scale (NRS), McGill Pain Questionnaire (SF -MPQ), Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). Serum concentrations of MMP-2 and TIMP-2 were measured by using the immunoenzymatic method. There was a significantly higher MMP-2 expression (medians: 4797.49 vs. 2656.65; p < 0.0001) and TIMP-2 concentration (medians: 166.40 vs. 109.60; p < 0.0001) in the DH compared to the CG. Significantly higher MMP-2 expression (4219.95 vs. 2656.65; p < 0.0001) and TIMP-2 concentration (medians: 150.17 vs. 109.60; p = 0.0003) were also found in the FBSS compared to the CG. The activity of MMP-2, measured as MMP-2/TIMP-2, did not significantly change between the DH, FBSS, and CG. MMP2 expression (p < 0.0001) and TIMP-2 concentration (p < 0.0001) were significantly higher in the DH than FBSS. Results indicate the presence of a contribution of MMP-2 and TIMP-2 in DH and FBSS. Unchanged activity of MMP-2 can indicate an insufficiency in the MMP-2 repair system in both diseases. Lower MMP-2 expression and TIMP-2 concentration in the FBSS group can reflect the chronicity of the process.

Taif Rose Oil Ameliorates UVB-Induced Oxidative Damage and Skin Photoaging in Rats via Modulation of MAPK and MMP Signaling Pathways.

Short-wave UVB (ultraviolet B) causes rapid oxidative damage to the skin. Rose water is obtained mainly from the petals of Rosa damascena Mill. (Rosaceae) and used traditionally to hydrate dry skin and reduce signs of aging. This work aimed at evaluating the possible protective potential of the prepared eco-friendly Taif rose oil nanoemulsion (ROSE-NANO) against UVB-induced photoaging in adult male Wistar rats. Taif rose oil (ROSE) was obtained from R. damascene by classical steam distillation and formulated in emulgel (100 mg/g). In addition, the oil was formulated in ROSE-NANO-loaded emulgel (50 and 100 mg/g) to enhance the effect of ROSE. All prepared formulas were tested topically for their potential protective effect in UV-induced skin photoaging. The obtained results demonstrated that application of ROSE-NANO-loaded emulgel resulted in superior antiaging potency over ROSE emulgel based on histological studies as well as biochemical evaluations via amendment in CAT and SOD activities, decreasing the concentration of the inflammatory markers and preventing collagen fragmentation through reduction of MMP-9 content in fibroblasts. Moreover, a significant decrease in mRNA expression of NF-KB, JNK, ERK1/2, and p38 MAPK genes was observed. In conclusion, the current study provides scientific evidence for the traditional use of rose oil in skin aging. Moreover, the NANO formula showed promising efficacy as a skin photoprotector against UV-induced oxidative damage and skin aging.

Imbalance of the protease-antiprotease system against the background of chronic obstructive pulmonary disease in combination with ischemic heart disease

The aim of the study: to evaluate the clinical value of the violation of the expression level of MMP-9 and TIMP against the background of chronic obstructive pulmonary disease (COPD) in combination with ischemic heart disease (IHD). Materials and methods. In accordance with the set goal of the study, 26 people with COPD + IHD and 22 practically healthy people were under observation. The average age of patients was 56.68 ± 1.21 years; 76.92 % were men. In the control group, the average age was 54.37 ± 1.84 years, 72.73 % were men. The object of the study was ischemic heart disease: angina pectoris. Research methods: external respiration function study, six minute walk test, determination of heart rate variability, the concentration of MMP-9 and TIMP in blood serum was determined by the method of solid-phase enzyme immunoassay. Results. The analysis of the level of expression of proteases and its inhibitor shows that patients with comorbid IHD on the background of COPD demonstrated 8.11 times higher activity of MMP-9 (p &lt; 0.05) compared to a cohort of practically healthy people. Indicators of TIMP activity in patients with IHD on the background of COPD are 1.46 ± 0.03 μg/ml, which is statistically significantly lower by 53.21 % (p &lt; 0.05) compared to healthy people (3.12 ± 0.01 μg/ml). The presence of reliable correlations between the MMP-9 level and the FEV1 indicator (r = -0.67, p &lt; 0.05), the LF/HF parameter (r = -0.74, p &lt; 0.05) indicates, that when the level of expression of MMP-9 is elevated, there is a more pronounced violation of the function of external respiration and a shift in the sympatho-parasympathetic balance in the direction of sympathetic activation and a decrease in vagal tone in heart rate modulation. The analysis of the meeting frequency with the analysis of conjugation tables showed that in persons in the upper quartile of MMP-9, prognostically negative parameters of the function of external breathing – an isolated decrease in the Tifno index (χ2 = 5.2 at p = 0.03), as well as the expressiveness of shortness of breath – were recorded more often ≥6 points on the Borg scale when assessing exercise tolerance during the 6-minute walk test (χ2 = 7.3 at p = 0.02). Conclusions. The obtained data demonstrate that patients with IHD on the background of COPD have a pronounced proteolytic imbalance and disruption of fibrotic processes compared to practically healthy individuals.

Regulatory T lymphocytes and selected cytokines in horses with mild to severe equine asthma and different inflammatory cytology profiles

This study determined Tregs and inflammatory cytokines in BALF and peripheral blood (PB) of adult horses with mild and severe asthma and different BALF cytological inflammation profiles. Horses of diverse breeds with asthma (age range: 2–20 years, n = 24) were divided into groups according to the number of points obtained in a standardized clinical scoring system (mild-moderate equine asthma – MEA, severe equine asthma – SEA) and according to the inflammation type based on cytological finding. Plasma levels of IFN-γ, IL-4, IL-10, IL-17 and MMP-9 in the BALF were determined by ELISA. Tregs in the BALF and PB were detected by flow cytometry. Horses with SEA were older than horses with MEA and had higher concentrations of MMP-9 in the BALF (P < 0.05). The neutrophilic inflammation group was characterised by higher age, grade of clinical score, percentage of Tregs and MMP-9 concentration in the BALF compared to the mastocytic inflammation group (P < 0.05). Age positively correlated with neutrophils, grade of score, Tregs in the BALF and in the PB. The grade of score positively correlated with MMP-9. The percentage of Tregs in the BALF positively correlated with Tregs in the PB. Tregs in the BALF and PB positively correlated with neutrophils and MMP-9 in the BALF and with IFN-γ, IL-4 and IL-10 in the plasma. IFN-γ and IL-10 in the plasma positively correlated with the age. The results indicate that the evaluation of selected parameters in PB, the collection of which is less invasive than the collection of BALF, is of potential importance.

Low-Grade Inflammatory Mediators and Metalloproteinases Yield Synchronous and Delayed Responses to Mechanical Joint Loading.

Mechanical loading is an essential factor for the maintenance of joint inflammatory homeostasis and the sensitive catabolic-anabolic signaling cascade involved in maintaining cartilage tissue health. However, abnormal mechanical loading of the joint structural tissues can propagate joint metabolic dysfunction in the form of low-grade inflammation. To date, few studies have attempted to delineate the early cascade responsible for the initiation and perpetuation of stress-mediated inflammation and cartilage breakdown in human joints. Fifteen healthy human male participants performed a walking paradigm on a cross-tilting treadmill platform. Blood samples were collected before exercise, after 30 minutes of flat walking, after 30 minutes of tilted walking, and after an hour of rest. Serum concentrations of the following biomarkers were measured: interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor alpha (TNF)-α, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, MMP-13, transforming growth factor beta (TGF)-β, tissue inhibitor of matrix metalloproteinase 1 (TIMP)-1, and cartilage oligomeric protein (COMP). Luminex Multiplex analysis of serum showed increased concentrations of COMP, IL-1β, TNF-α, IL-10, and TGF-β from samples collected after flat and cross-tilted treadmill walking compared to baseline. Serum concentrations of MMP-1 and MMP-13 also increased, but primarily in samples collected after tilted walking. Pearson's correlation analysis showed positive correlations between the expression of COMP, TNF-α, IL-10, and MMP-13 at each study timepoint. Stress-mediated increases in serum COMP during exercise are associated with acute changes in pro and anti-inflammatory molecular activity and subsequent changes in molecules linked to joint tissue remodeling and repair.

The Effect of PCSK9 Inhibition on the Stabilization of Atherosclerotic Plaque Determined by Biochemical and Diagnostic Imaging Methods.

Atherosclerosis is a multifactorial, progressive, chronic inflammatory disease. Ultrasound and magnetic resonance imaging are the most accurate predictors of atherosclerotic plaque instability (MRI). Cytokines such as osteopontin, osteoprotegerin, and metalloproteinase 9 could be used as the most recent markers to identify and track the efficacy of anti-atherosclerotic therapy. Patients with USG and MRI-verified unstable atherosclerotic plaque were included in the study. Biomarker concentrations were measured and compared before and after PCSK9 inhibitor therapy. Additionally, concentrations prior to treatment were correlated with MRI images of the carotid artery. After treatment with alirocumab, the concentrations of MMP-9 (p < 0.01) and OPN, OPG (p < 0.05) decreased significantly. Furthermore, the results of OPN, OPG, and MMP 9 varied significantly depending on the type of atherosclerotic plaque in the MRI assay. In stable atherosclerotic plaques, the concentrations of OPN and OPG were greater (p < 0.01), whereas the concentration of MMP9 correlated with the instability of the plaque (p < 0.05). We demonstrated, probably for the first time, that alirocumab therapy significantly decreased the serum concentration of atherosclerotic plaque markers. In addition, we demonstrated the relationship between the type of atherosclerotic plaque as determined by carotid MRI and the concentration of these markers.

Association between FGA gene polymorphisms and coronary artery lesion in Kawasaki disease.

To investigate the correlation between FGA gene polymorphisms and coronary artery lesion in Kawasaki disease. Two hundred and thirty four children with Kawasaki disease (KD group), 200 healthy children (normal group) and 208 children with non-KD fever (fever group) were enrolled. General clinical indicators, the concentration of serum MMPs, TIMP-1, FG-α,fibrinogen level, molecular function (FMPV/ODmax) and FGA Thr312Ala polymorphism were detected individually by testing peripheral venous blood after fasting in the morning. There was no significant difference in average age among the three groups, which were 3.03 ± 1.22 years, 3.17 ± 1.30 years, and 3.21 ± 1.31 years, respectively. Compared with those in the fever group, the levels of white blood cell count (WBC), platelet count (PLT), procalcitonin (PCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and fibrinogen (Fg) levels were significantly increased in the KD group. Red blood cell count (RBC) and hemoglobin (Hb) levels were significantly decreased (p < 0.05).The concentration of serum MMPs, TIMP-1, and FG-α in the KD and fever groups were significantly higher than those in the normal group (p < 0.05). The concentration of MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and FG-α in the KD group were significantly higher than those in the fever group (p < 0.05).The KD group was divided into two subgroups,55 patients with combined CAL and 179 patients without combined CAL. The plasma fibrinogen concentration in the combined CAL group was significantly higher than that in the non-combined CAL and normal groups (p < 0.01). There was no statistically significant difference in FMPV/ODmax among the three groups (p > 0.05). Compared with normal group, the FGA GG, GA, and AA genotype and G, A allele frequency of the FGA gene polymorphism in the KD group showed no significant difference (p > 0.05). In the KD group, the most common type in children with CAL was GA, while the most common type in children without CAL was GG. MMPs and FG-α were significantly upregulated in KD patients. The proportion of FGA genotype GA in children with CAL was significantly higher than that in children without CAL, suggesting that FGA gene polymorphisms affect coronary artery lesion in children with KD.

Assessing effects of mechanical stimulation of fluid shear stress on inducing matrix Metalloproteinase-9 in cultured corneal epithelial cells

Blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells. Therefore, we evaluated whether fluid shear stress affects matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human corneal epithelial cells (HCECs). No other study has shown the influence of fluid shear stress on HCECs regarding mRNA expression and the protein levels of MMPs. Cultured HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) for 12 and 24 h with the parallel-plate type of flow chamber. Gene expression of MMPs and TIMPs was measured by real-time polymerase reaction. Concentrations of MMP-1 and MMP-9 in cell lysates were determined using bead-based amplified luminescent proximity homogenous assay-linked immunosorbent assay. The expression of MMP-9 and MMP-1 in HCECs exposed to low and high flow for 12 and 24 h, respectively, increased significantly compared with those under static conditions. The expression of MMP-9 in the cells exposed to high flow for 24 h increased significantly compared with those under static and low flow conditions. Levels of MMP-9 in cell lysates exposed to fluid flow for 24 h were elevated significantly with increasing shear stress. Fluid shear stress exerted on HCECs affected MMPs, which was associated with inflammation and pathogenesis. Mechanical stress induced by blinking might influence expression of MMPs on the ocular surface. Further studies are warranted to establish the molecular mechanism of shear stress-induced alternations of MMPs.

Role of Angiopoietic Coronary Endothelial Dysfunction in the Pathogenesis of Ischemic Cardiomyopathy.

The angiopoietic endothelial dysfunction in ischemic cardiomyopathy (ICMP) remains unexplored. The identification of the imbalance of endothelial dysfunction mediators and the number of endothelial progenitor (EPC) and desquamated (EDC) cells in patients with coronary heart disease (CHD) with and without ICMP. A total of 87 patients (47 with ICMP and 40 without ICMP) were observed. The content of EPCs (CD14+CD34+VEGFR2+) in vein blood and EDCs (CD45-CD146+) in the blood from the coronary sinus and cubital vein was determined by flow cytometry. The contents of HIF-1α and HIF-2α in vein blood as well as that of ADMA and endothelin-1 in sinus plasma and angiopoietin-2, MMP-9 and galectin-3 in both samples were assessed using ELISA, and VEGF, PDGF, SDF-1 and MCP-1 contents using immunofluorescence. ADMA and endothelin-1 levels in the sinus blood were comparable between the patient groups; a deficiency of HIF-1α and excess of HIF-2α were detected in the vein blood of ICMP patients. The EDC content in the vein blood increased in CHD patients regardless of ICMP, and the concentrations of VEGF-A, VEGF-B, PDGF, MCP-1, angiopoietin-2, and MMP-9 were normal. In ICMP patients, vein blood was characterized by an excess of galectin-3 and sinus blood by an excess of EDCs, angiopoietin-2, MMP-9 and galectin-3. ICMP is accompanied by angiopoietic endothelial dysfunction.

Paper 36: Levels of Synovial Fluid Cytokines Predict Midterm Patient Reported Outcomes Following Arthroscopic Partial Meniscectomy

Objectives: To identify synovial fluid biomarkers associated with midterm postoperative outcomes in patients undergoing arthroscopic partial meniscectomy (APM). Methods: Subjects were prospectively enrolled in a cohort of patients who had synovial fluid aspirated from their knee on the day of surgery prior to undergoing APM. Biomarker analysis was performed. Preoperative patient-reported outcome (PRO) scores including VAS pain, Lysholm and Tegner activity score were collected preoperatively. At a minimum of 2 years of follow-up postoperative outcomes were collected. Using previously described values, patients who met the minimal clinically important difference (MCID) for Lysholm score were identified and groups were compared using parametric and non-parametric tests. Using preoperative and postoperative outcome scores, generalized linear models were used to explore the relationship between biomarkers and improvement in Lysholm Score, improvement in visual analog scale (VAS) pain score, and postoperative KOOS-PS. Results: Fifty patients were included in the study. 34 (68%) met the MCID for the Lysholm score and 16 (32%) did not. Mean age was 51 ± 9 years for the entire cohort, with no statically significant differences between the groups (p=0.35). Both groups were majority male (p=0.37) and there were no differences in BMI (0.74) or follow-up time (p=0.20). On logistic regression, increased concentration of RANTES (β = -6.30, p = 0.04) and MMP-3 (β = -15.16, p = 0.001) were predictive of less improvement in VAS pain. . For Lysholm score, higher SF levels of IL-1 RA were predictive of greater improvement (β = 12.57, p = 0.04) while higher levels of MMP-3 were predictive of reduced improvement (β = -10.34, p = 0.007). Conclusions: This study found that at the time of surgery, intraarticular levels of MMP-3 and RANTES are predictive of poorer midterm outcomes and higher pain levels following APM. Additionally, higher levels of IL-1RA at the time of surgery were associated with greater improvement in midterm Lysholm score.

Urinary Cytokines as Potential Biomarkers of Mild Cognitive Impairment and Alzheimer's Disease: A Pilot Study.

Alzheimer's disease (AD) is the most common form of dementia, accounting for 80% of all cases. Mild cognitive impairment (MCI) is a transitional state between normal aging and AD. Early detection is crucial, as irreversible brain damage occurs before symptoms manifest. This study aimed to identify potential biomarkers for early detection of AD by analyzing urinary cytokine concentrations. We investigated 37 cytokines in AD, MCI, and cognitively normal individuals (NC), assessing their associations with AD development. Urinary cytokine concentrations were measured in AD (n = 25), MCI (n = 25), and NC (n = 26) patients. IL6ST and MMP-2 levels were compared between AD and NC, while TNFRSF8, IL6ST, and IL-19 were assessed in AD versus MCI. Diagnostic models distinguished AD from NC, and in-silico analysis explored molecular mechanisms related to AD. Significant perturbations in IL6ST and MMP-2 concentrations were observed in AD urine compared to NC, suggesting their potential as biomarkers. TNFRSF8, IL6ST, and IL-19 differed significantly between AD and MCI, implicating them in disease progression. Diagnostic models exhibited promising performance (AUC: 0.59-0.79, sensitivity: 0.72-0.80, specificity: 0.56-0.78) in distinguishing AD from NC. In-silico analysis revealed molecular insights, including relevant non-coding RNAs, microRNAs, and transcription factors. This study establishes significant associations between urinary cytokine concentrations and AD and MCI. IL6ST, MMP-2, TNFRSF8, IL6ST, and IL-19 emerge as potential biomarkers for early detection of AD. In-silico analysis enhances understanding of molecular mechanisms in AD. Further validation and exploration of these biomarkers in larger cohorts are warranted to assess their clinical utility.

Analysis of MMP-2-735C/T (rs2285053) and MMP-9-1562C/T (rs3918242) Polymorphisms in the Risk Assessment of Developing Lung Cancer

Matrix metalloproteinase (MMP)-2 and -9 are gelatinases which are capable of degrading type IV collagen and have been linked to cancer invasion and metastatic development. MMP-2 and MMP-9 gene polymorphisms may affect their biological function, and thus their role in cancer development and progression. We analyzed the association of the polymorphism frequencies of MMP-2-735C/T and MMP-9-1562C/T with MMP-2 and MMP-9 serum concentrations, as well as their potential effects in lung cancer patients. We conducted a retrospective, case-control study consisting of 112 lung cancer patients and 100 healthy individuals from a Caucasian population in Poland. Polymerase chain reaction with restriction fragment length polymorphism (PCR/RFLP) and electrophoresis was used to genotype genomic DNA from whole blood samples. MMP-2 and MMP-9 serum concentrations were then determined using ELISA. For statistical analysis, Statistica version 13 from TIBCO Software Inc. was utilized with a significance level &lt;0.05. Logistic regression analysis revealed that MMP-2-735CC (OR = 5.39; 95% CI = 0.62–47.17; p = 0.238504) and -735CT genotype (OR = 7.22; 95% CI = 0.78–67.14; p = 0.072836), as well as MMP-9-1562CC (OR = 1.45; 95% CI = 0.31–6.70; p = 0.757914) and -1562CT genotype (OR = 1.60; 95% CI = 0.33–7.83; p = 0.548801) were associated with a higher risk of lung cancer. There were statistically significant differences observed in the MMP-2 concentration between individuals with the -735CC genotype and the -735CT genotype (non-smoking control: 204.04 ng/mL vs. 237.00 ng/mL, respectively, p = 0.041479; adenocarcinoma patients: 157.69 ng/mL vs. 126.37 ng/mL, respectively, p = 0.013222), as well as differences in the MMP-9 concentration between individuals with the -1562CC genotype and the -1562CT genotype (smoking control: 385.67 ng/mL vs. 562.80 ng/mL, respectively, p = 0.000936; patients with other lung neoplasms: 821.64 ng/mL vs. 928.88 ng/mL, respectively p = 0.023315). The role of MMP-2-735C/T and MMP-9 -1562C/T polymorphisms in an increased risk of lung cancer cannot be dismissed. Specific genotypes affect MMP-2 and MMP-9 concentrations in both lung cancer patients and healthy controls, which may thereby increase lung cancer risk, disease aggressiveness, and patient survival outcomes.

Relationship between the salivary concentration of matrix metalloproteinases 8 and 20 and severe early childhood caries.

Dental caries is initiated through mineral dissolution by bacterial acids and collagen degradation by endogenous proteolytic enzymes, mainly collagenolytic matrix metalloproteinases (MMPs). The present research aimed to evaluate the relationship between severe early childhood caries (S-ECC) and salivary MMP-8 and MMP-20 concentrations. Fifty children aged 36-60 months were assigned to either the caries-free (control) group or the S-ECC group. Standard clinical examinations were performed, and approx. 1 mL of expectorated unstimulated whole saliva was collected from all participants. In the S-ECC group, the sampling was repeated 3 months after restorative treatment. All samples were analyzed for the salivary concentrations of MMP-8 and MMP-20, using the enzyme-linked immunosorbent assay (ELISA). Statistical analysis employed the t test, the Mann-Whitney U test, the χ2 test, Fisher's exact test, and the paired samples t test. The level of significance was set at 0.05. At baseline, the subjects in the S-ECC group presented with significantly elevated levels of MMP-8 as compared to the control group. However, the salivary concentration of MMP-20 did not exhibit a significant difference between the 2 groups. A significant reduction occurred in the levels of MMP-8 and MMP-20 3 months after restorative treatment in the S-ECC group. The salivary levels of MMP-8 and MMP-20 were significantly affected by dental restorative treatment in children. Furthermore, MMP-8 was observed to be a better indicator of the dental caries status than MMP-20.

Clinical value of combined serum MMP-2, MMP-9 and TIMP-1 for the prognosis of perianal fistula patients who received minimally invasive surgery.

This study aimed to investigate the clinical value of combined serum matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) for the prognosis of perianal fistula patients. Patients diagnosed and treated for perianal fistula by minimally invasive surgery (MIS) were enrolled. The concentrations of serum MMP-2, MMP-9 and TIMP-1 were measured at 24 h after surgery. Different levels of wound secretion, growth of granulation tissue and wound pain were used as criteria to evaluate surgical incision healing. The receiver operating characteristic curve was used to analyze the predicted assessment value. The concentrations of serum MMP-2 and MMP-9 were significantly higher, while the concentrations of serum TIMP-1 at 24 h after surgery were significantly lower in the poor healing group than in the good healing group. It was further found that high levels of serum MMP-2 and MMP-9 were risk factors for poor healing, while high concentrations of serum TIMP-1 at 24 h after surgery were protective factors for poor healing. High concentrations of serum MMP-2 and MMP-9 and low concentrations of serum TIMP at 24 h after surgery are risk factors for poor healing in perianal fistula patients who receive MIS, and the combined test has a higher predictive value.

Porphyromonas gingivalis induces cardiovascular dysfunction.

Porphyromonas gingivalis (P. gingivalis) is one of the most responsible periodontopathogenic bacteria in the development of periodontal disease (PD); however, its role in the development of other diseases still needs to be understood, specially its implications in the causation of cardiovascular pathogenesis. The aim of this study is to determine whether there is a direct association between P. gingivalis-induced PD with that of the development of cardiovascular disease, and whether a long-term administration of probiotic(s) could help improve the cardiovascular disease outcome. To test this hypothesis, we employed four different experimental groups of mice, designated as: Group I: Wild-type (WT) mice (C57BL/6J); Group II: Lactobacillus rhamnosus GG (LGG) (WT mice treated with a probiotic; LGG), Group III: PD (WT mice treated with P. gingivalis), and Group IV: PD+LGG (WT mice treated with P. gingivalis and LGG). PD was created by injecting 2 µL (i.e., 20 µg) of P. gingivalis lipopolysaccharide (LPS) intragingivally between the 1st and 2nd mandibular molars, two times a week for a total period of 6 weeks. The PD (LGG) intervention was done orally employing 2.5× 105 CFU/day for a continuous period of 12 weeks. Immediately before the mice were sacrificed, echocardiography of the heart was performed, and after sacrifice, we collected serum samples, hearts, and the periodontal tissue. Histological assessment, cytokine analysis, and zymography of the cardiac tissue were performed. Results revealed inflammation of the heart muscle in the PD group that was marked by infiltration of neutrophils and monocytes, followed by fibrosis. Cytokine analysis of the mice sera revealed significantly elevated levels of tumor necrosis factor-α, IL-1β, IL-6, and IL-17A in the PD group along with LPS-binding protein, and CD14. Most importantly, we observed elevated levels of P. gingivalis mRNAs in the heart tissues of PD mice. Zymographic analysis demonstrated matrix remodeling as revealed by increasing content of MMP-9 in the heart tissues of PD mice. Interestingly, LGG treatment was able to mitigate most of the pathological effects. The findings suggest that P. gingivalis could lead to cardiovascular system disorder and that probiotic intervention could alleviate, and most likely prevent bacteremia and its harmful effect(s) on the cardiovascular function.

Serum Concentration of MMP-9 as a Predictive Biomarker for the Progression of Oral Cancer.

Oral cancer is the most prominent cancer subtype among all head and neck cancers, the incidence and prevalence of which has been consistently increasing in past years around the globe. At advanced stages, oral cancer imparts significant mortality, morbidity, and mutilation among the patients, and therefore, diagnosis and treatment of the disease at early stages are considered the optimum strategy for the management of the disease. Since molecular changes appear earlier than physical symptoms, several molecular biomarkers are currently being investigated for their role in diagnosing and treating disease. MMP-9 belongs to the family of proteinases that are involved in cytoskeletal degradation, which is a crucial phase of cancer progression. In the present study, we analyzed the serum concentration of MMP-9 in oral cancer patients and tried to establish MMP-9 as a predictive biomarker for the progression of oral cancer.We also correlated the clinical, sociodemographic andbiochemical parameters with the serum concentration of MMP-9 in oral cancer patients. Serum was extracted from the blood sample of 38 oral cancer patients and was analyzed for the concentration of MMP-9 using sandwiched ELISA.Predesigned proforma was used to capture the clinical, sociodemographic and biochemical parameters. Unpaired t-test was used to compare two means, one way ANOVA was used to compare more than two means and Pearson's correlation was used to correlate the variables. The mean concentration of MMP-9 in patients of oral cancer was 816.9 ± 236.1ng/mL. The MMP-9 expression level was higher at advanced oral cancer stages than in the early stages. No significant difference in theMMP expression was found in terms ofsociodemographic risk factorand tumor site. MMP-9 exhibit significant negativecorrelation with the HDLand significantly positive correlation with the PTI. Rest of thebiochemical parametersdoes not exhibit significant correlation. The present study suggests that serum concentration of MMP-9 can be a predictive biomarker for the progression of oral cancer, which needs to be validated by performing further longitudinal cross-sectional studies by taking ample sample size.

Prospective assessment of cytokines and regulatory proteins concentration in the tear fluid of POAG patients with various hypotensive effects after non-penetrating deep sclerectomy

The aim. To assess the dynamics of cytokine content in tear fluid of primary openangle glaucoma (POAG) patients at various terms after non-penetrating deep sclerectomy (NPDS) in relation to the functional state of the outflow tracts.Material and methods. We carried out prospective examination of 65 patients with advanced stage of primary open-angle glaucoma after NPDS. Depending on the course of the postoperative period and the conditions for achieving the hypotensive effect of NPDS, all patients were divided into three groups: group 1 – with the optimal hypotensive effect; group 2 – with the conditional hypotensive effect; group 3 – with no hypotensive effect after NPDS. The intraocular pressure and the concentration of TGF-β, MMP-9, IL-6, IL-8, VEGF-A (121 and 165) in the tear fluid were studied using ELISA method in pre- and postoperative period. We studied the outflow tracts using optical coherence tomography and carried out ultrastructural analysis of filtering blebs tissue.Results. In group 1, the minimum initial concentrations of IL-6, IL-8 and TGF-β in the tear fluid and their moderate increase in the postoperative period; high concentrations of MMP-9 at all stages and an increase in VEGF-A by 2 months after NPDS were registered. In group 2, there was a high level of VEGF-A in the tear fluid before and 2 months after NPDS, an increase in TGF-β, IL-6 and IL-8 in the tear fluid in the early period with their suppression in the late period, as well as an increase in MMP-9 in the early postoperative period. Group 3 had maximum concentrations of TGF-β and IL-8 in the tear fluid initially and in the early postoperative period, suppression of MMP-9 in the tear fluid 2 weeks after and of VEGF-A 2 months after NPDS.Conclusion. Initially high concentrations of IL-6, IL-8, and TGF-β in the tear fluid and the suppression of MMP-9 and VEGF-A in the postoperative period contribute to the surgical failure of the NPDS.