MMP-9 Concentrations Research Articles

Peptide Selection of MMP-1 for Electrochemical Sensing with Epitope-Imprinted Poly(TPARA-co-EDOT)s.

Instead of molecularly imprinting a whole protein molecule, imprinting protein epitopes is gaining popularity due to cost and solubility issues. Belonging to the matrix metalloproteinase protein family, MMP-1 is an interstitial collagenase that degrades collagen and may be involved in cell migration, cell proliferation, the pro-inflammatory effect, and cancer progression. Hence, it can serve as a disease protein biomarker and thus be useful in early diagnosis. Herein, epitopes of MMP-1 were identified by screening its crystal structure. To identify possible epitopes for imprinting, MMP-1 was cleaved in silico with trypsin, pepsin at pH = 1.3, and pepsin at pH > 2.0 using Peptide Cutter, generating peptide fragments containing 8 to 12 amino acids. Five criteria were applied to select the peptides most suitable as potential epitopes for MMP-1. The triphenylamine rhodanine-3-acetic acid (TPARA) functional monomer was synthesized to form a stable pre-polymerization complex with a selected template epitope. The complexed functional monomer was then copolymerized with 3,4-ethoxylenedioxythiophene (EDOT) using potentiodynamic electropolymerization onto indium-tin-oxide (ITO) electrodes. The composition of the molecularly imprinted poly(TPARA-co-EDOT) (MIP) was optimized by maximizing the film's electrical conductivity. Cyclic voltammetry was used to determine MMP-1 concentration in the presence of the Fe(CN)63-/Fe(CN)64- redox probe actuating the "gate effect." A calibration curve was constructed and used to determine the usable concentration range and the limit of detection as ca. 0.001 to 10.0 pg/mL and 0.2 fg/mL MMP-1, respectively. Finally, the MMP-1 concentration in the A549 human lung (carcinoma) culture medium was measured, and this determination accuracy was confirmed using an ELISA assay.

Comparison of Concentrations of MMP2 and MMP9 in Aqueous Humor of Patients Suffering with Acute Primary Angle Closure Short Title: MMPs and acute primary angle closure

Comparison of Concentrations of MMP2 and MMP9 in Aqueous Humor of Patients Suffering with Acute Primary Angle Closure Short Title: MMPs and acute primary angle closure

Matrix Metalloproteinases in Pathogenesis of Ventilation Disorders of the Respiratory System in Patients with Chronic Pulmonary Tuberculosis

The imbalance in matrix metalloproteinase (MMP)/inhibitors system leads to degradation of extracellular matrix of connective tissue and pathological remodeling forming the morphological basis for respiratory dysfunction.The objective: to study the relationship between parameters of MMP/inhibitors system in blood and parameters of ventilation and gas exchange disorders in patients with chronic pulmonary tuberculosis (PTB).Subjects and Methods. Patients with the verified diagnosis of tuberculoma (n = 45) and fibrous-cavernous pulmonary tuberculosis (n = 85) were examined. All patients underwent computed tomography of the chest and assessment of respiratory function. Serum concentrations of MMP-1, -3, -8, -9 and their inhibitors TIMP-1 and α2-macroglobulin (MG) were tested by ELISA (R&D Systems, Minneapolis, MN, USA). Statistica 7.0 and an ANCOVA model were used for statistical analysis which considered the diagnosis and smoking status as factors, and the respiratory function parameters were considered as covariates.Results. In pulmonary tuberculosis patients, the concentrations of MMP-9 and MMP-8 in the blood correlated with extension of lung parenchyma lesions when compared to tuberculomas and fibro-cavernous tuberculosis, MMP-9 and TIMP-1 with changes in lung volumes (R2 = 0.60 and 0.80; p = 0.001), and MMP-8 correlated with functional disorders of gas exchange (R2 = 0.60 and 0.80; p = 0.001). Changes in MMP-1, MMP-3, and α2-MG (R2 = 0.60 and 0.80; p = 0.45) did not correlate with extension of lung parenchymal lesions and decreased lung function.

Association between transforming growth factors-β and matrix metalloproteinases in the aqueous humor and plasma in myopic patients

To investigate the relationship between levels of transforming growth factor beta (TGF-beta), matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP) in the aqueous humor (AH) and plasma (PL) of myopic patients. Aqueous humor and plasma were collected intraoperatively from 37 myopic patients with various axial lengths (AL) during ICL surgery. The concentrations of TGF-β1, TGF-β2, TGF-β3, MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were measured using Luminex xMAP Technology kits (Milliplex xMAP kits). The association between TGFβ and MMP/TIMP levels were analyzed based on the Spearman's correlation test or Pearson's correlation test. There was a negative correlation between TGF-β1 and MMP-1, TIMP-2, TIMP-3 and TIMP-4 in the AH, and a positive correlation between TGF-β1 and MMP-1 in the PL. In the AH, levels of TGF-β2 were positively correlated with levels of TIMP-3 (r=0.441; P<0.001). In the PL, levels of TGF-β2 also correlated positively with levels of TIMP-3 (r=0.427; P<0.001)). The level of TGF-β2 was the highest among TGF-βs in the AH. A consistent positive correlation between TGF-β2 and TIMP-3 was found both in the AH and PL, indicating that systemic levels of TGF-β2 and MMPs/TIMPs may also play a role in myopic progression.

Therapeutic Applications of Garlic and Turmeric for the Diabetic Wound Healing in Mice.

Diabetes is involved in delayed wound healing that can be cured by natural products such as garlic, turmeric, and fibroin extracts. Alloxan monohydrate is used for inducing diabetes in mice. The percent wound contraction of garlic (150 mg/ml), turmeric (100 mg/ml), and fibroin (50 mg/ml), individually and in combinations garlic (150 mg/ml) + fibroin (50 mg/ml), turmeric (100 mg/ml) + fibroin (50 mg/ml), garlic (150 mg/ml) + turmeric (100 mg/ml), and garlic (150 mg/ml) + turmeric (100 mg/ml) + fibroin (50 mg/ml) was checked by evaluating the healing time, % wound contraction and histological analysis. The serum level of MMPs (MMP 2, MMP7, MMP 9), pro-inflammatory cytokines (TNF-α, IL-6, IL-8), and TIMPs were evaluated. With the combination of three extracts (Ga+Tu+Fi) garlic (150 mg/ml), turmeric (100 mg/ml) and fibroin (50 mg/ml), wounds healed in 12 days and had 97.3 ± 2.2% wound contraction. While the positive control (polyfax) and diabetic control (saline) wounds healed in 17- and 19-days with wound contraction of 96.7 ± 1.4% and 96.3 ± 1.1%, respectively. Histological analysis showed that the combination of Ga+Tu+Fi exhibited an increase in the growth of collagen fibers, fibroblasts number, and keratinocytes, and lessened inflammation of blood vessels. The combination of Ga+Tu+Fi significantly alleviated the serum concentration of TNF-α (14.2 ± 0.7 pg/ml), IL-6 (10.0 ± 1.0 pg/ml), IL-8 (16.0 ± 1.5 pg/ml), MMP2 (228.0 ± 18.1 pg/ml), MMP7 (271.0 ± 9.9 pg/ml), and MMP9 (141.0 ± 5.3 pg/ml) to diabetic control. The level of TIMPs (193.0 ± 9.1 pg/ml) was increased significantly with respect to diabetic control. We conclude that the combination of these biomaterials possessed high regenerative and healing capabilities and can be an effective remedy in the healing of chronic wounds in diabetic patients.

The Concentration of Fibronectin and MMP-1 in Patients with Alzheimer's Disease in Relation to the Selected Antioxidant Elements and Eating Habits.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common form of dementia in the elderly. In recent years, markers of this disease have been researched, with an emphasis on prophylaxis. The aim of this study is to evaluate the concentration of fibronectin and MMP-1 in serums in relation to levels of antioxidant elements, as well as eating habits in the group of patients with AD (n = 110). The control group consisted of 60 healthy people. The conducted studies showed that patients with AD are characterized by a significantly higher median concentration of fibronectin compared to healthy subjects (652.06 vs. 268.31 µg/mL), but a significantly lower median of MMP-1 (4.62 vs. 18.09 ng/mL). Significant inverse correlations between MMP-1 and the concentration of antioxidant elements, as well as positive correlations between MMP-1 vs. Total Antioxidant Status (TAS) and MMSE, were observed. Multiple regressions showed that the concentration of fibronectin can be explained in 28% cases by eating habits, and by MMP-1 in 25%. Nutritional modifications to reduce the consumption of fruit, meat and processed products can be part of AD prevention.

Metalloproteinases and Tissue Inhibitors in Generalized Myasthenia Gravis. A Preliminary Study.

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have recently been proposed as promising biomarkers in different immune-mediated disorders. We evaluated the plasma levels of MMP-9 and MMP-2 and their tissue inhibitors TIMP-1 and TIMP-2 in a patients' cohort with generalized myasthenia gravis (MG). Plasma concentrations of MMP-9, MMP-2, TIMP-1 and TIMP-2 were evaluated in 14 patients with generalized MG and 13 age- and sex-matched healthy controls. The severity of disease was assessed by the modified Osserman classification. Compared to the healthy subjects, MG patients had increased plasma concentrations of MMP-9, but reduced plasma levels of MMP-2 and TIMP-1. MG patients also showed a positive correlation between MMP-2 concentrations and disease severity. An increase in MMP-9 levels and MMP-9/TIMP-1 ratio and a decrease in MMP-2 levels and MMP-2/TIMP-2 ratio were detected in patients with generalized MG. Higher levels of MMP-2 correlated with greater disease severity. Our preliminary findings suggest that MMPs and TIMPs could play a role in the pathogenesis of MG and might be associated with the risk of clinical deterioration.

Effect of Increasing Body Mass Index On the Activity of Matrix Metalloproteinase-2

The Increasing Body Mass Index is one of the major concerns in today's lifestyle, which may give rise to various disorders. Studies have suggested that Matrix Metalloproteinases (MMPs) are associated with Obesity and cardiovascular disease. This study aimed to evaluate the serum activity of Matrix Metalloproteinase-2 in overweight patients with anthropometric measurements to assess the effect of body mass index in MMP-2 activity. In this Age and sex matched case-control study the participants were selected in 2:1 ratio (219 cases and 108 controls). In this study Body Mass Index, Blood Pressure, and other biochemical parameters i.e. Fasting Blood Sugar (FBS), Total Cholesterol (TC), Triglycerides (TG), High-density lipoprotein cholesterol (HDL-C), Low-density lipoprotein cholesterol (LDL-C) along with MMP-2 were measured through semi-autoanalyzer and ELISA respectively. There was an increased concentration of FBS in overweight patients compared to the control group, which was statistically significant. In the case of lipid profile, there was an elevated concentration of TC, TG, and LDLC in the overweight population when compared to the control group and the findings were statistically significant, while HDL-C was significantly elevated in the control group compared to the case group. With respect to blood pressure, a significant increase was observed in systolic and diastolic blood pressure. In this study, there was a significant elevation of MMP-2 in the case group compared to the control group, which was positively associated with Body Mass Index. The outcome of this study revealed that increasing body weight might be the root cause of developing several life-threatening risk factors if not considered at initial level. Furthermore, altered concentration of MMP-2 in overweight patients may highlight cardiovascular Risk in these patients. (authors need to rewrite the abstract systematically. In addition, there are many spelling and grammatical errors.)Â

Rapid magnetic separation: An immunoassay platform for the SERS-based detection of subarachnoid hemorrhage biomarkers.

The blood-brain barrier (BBB) is of vital importance to the progression and prognosis of subarachnoid hemorrhage (SAH). The construction of a simple, sensitive, and accurate detection assay for measuring the biomarkers associated with BBB injury is still an urgent need owing to the complex pathogenesis of SAH and low expression levels of pathological molecules. Herein, we introduced surface-enhanced Raman scattering (SERS) label-embedded Fe3O4@Au core-shell nanoparticles as ideal SERS sensors for quantitative double detection of MMP-9 and occludin in SAH patients. Meanwhile, utilizing the SERS signals to dynamically estimate MMP-9 and occludin concentration in the rat SAH model is the first application in exploring the relationship of pathological MMP-9 and occludin molecular levels with neurobehavioral score. This method warrants reliable detection toward MMP-9 and occludin with a wide recognition range and a low detection limit in blood samples. Furthermore, the results monitored by the SERS assay exactly matched with those obtained through a traditional enzyme-linked immunosorbent assay (ELISA). The aforementioned results demonstrated this novel biosensor strategy has extensive application prospects in the quantitative measurement of multiple types of biomolecules in body fluid samples.

Two Laminaria japonica Fermentation Broths Alleviate Oxidative Stress and Inflammatory Response Caused by UVB Damage: Photoprotective and Reparative Effects.

UVB radiation can induce oxidative stress and inflammatory response in human epidermal cells. We establish a UVB-induced damage model of human immortalized epidermal keratinocytes (HaCaT) to explore the protective and reparative effects of Laminaria japonica on UVB-damaged epidermal inflammation after fermentation by white Ganoderma lucidum (Curtis) P. Karst and Saccharomyces cerevisiae. Compared with unfermented Laminaria japonica, fermented Laminaria japonica possesses stronger in vitro free radical scavenging ability. Laminaria japonica white Ganoderma lucidum fermentation broth (LJ-G) and Laminaria japonica rice wine yeast fermentation broth (LJ-Y) can more effectively remove excess reactive oxygen species (ROS) in cells and increase the content of the intracellular antioxidant enzymes heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1). In addition, fermented Laminaria japonica effectively reduces the content of pro-inflammatory factors ILs, TNF-α and MMP-9 secreted by cells. The molecular research results show that fermented Laminaria japonica activates the Nrf2 signaling pathway, increases the synthesis of antioxidant enzymes, inhibits the gene expression levels of pro-inflammatory factors, and alleviates cellular oxidative stress and inflammatory response caused by UVB radiation. Based on the above results, we conclude that fermented Laminaria japonica has stronger antioxidant and anti-inflammatory activity than unfermented Laminaria japonica, possesses good safety, and can be developed and used as a functional inflammation reliever. Fermented Laminaria japonica polysaccharide has a more slender morphological structure and more rockulose, with better moisturizing and rheological properties.

Acute response of biomarkers in plasma from capillary blood after a strenuous endurance exercise bout

PurposeThe present study aims to investigate the acute response of potential exercise-sensitive biomarkers in capillary plasma to an acute incremental running test. In a second step, their concentration was compared to the changes in the venous serum.MethodsThirty-seven active young female and male adults completed a VO2max ramp test on a treadmill. Before and after exercise, capillary blood from the earlobe and venous blood were taken and synchronized. Concentrations of Interleukin- (IL-) 1β, IL-1ra, IL-6, IL-8, IL-17A, Interferon (IFN)-y, CC-chemokine ligand (CCL)-2, Matrix metallopeptidase (MMP)-9, Secreted protein acidic and rich in cysteine (SPARC), Cluster of differentiation (CD)163, S100 Ca2+ -binding protein (S100) A8, S100A9, S100B, Brain-derived neurotrophic factor (BDNF), and Myeloperoxidase (MPO) were determined by magnetic bead-based multiplex assay.ResultsCapillary plasma concentrations of IL-1β, IL-6, IL-8, IL-17A, IFN-y, CCL-2, MMP-9, SPARC, CD163, S100A9, S100B, and BDNF increased after exercise (p < 0.05). Comparing the values from capillary plasma and venous serum, ICCs classified as good were found for IFN-y (post), while the ICCs for IL-1β, IL-8, IL-17A, CCL-2, MMP-9 (post), SPARC, and BDNF (post) were classified as moderate. For all other parameters, only weak ICCs were found.ConclusionAs in the venous serum, there was an increase in most markers in the capillary plasma. However, acceptable to low associations can be found in the concentration levels of these proteins between the compartments. Thus, this source of blood sampling could find some biomarker applications in sports practice.

TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals.

HTLV-1-infected individuals may develop a neurologic inflammatory condition known as HTLV-1-associated myelopathy (HAM/TSP), in which the high production of TNF is observed. These patients exhibit higher proviral loads, enhanced production of proinflammatory cytokines and lymphocyte proliferation in comparison to asymptomatic HTLV-1 carriers and those presenting overactive bladder (OAB-HTLV-infected). Metalloproteinases (MMPs) are known to degrade the components of the blood-brain barrier, favoring the migration of infected cells into the central nervous system. Moreover, the unbalanced production of MMPs and their inhibitors (TIMPs) has also been associated with tissue damage. The present work studied the production of MMP-9 and TIMPs in HTLV-1-infected individuals with and without neurological manifestations. HAM/TSP patients presented higher concentrations of MMP-9 in peripheral blood mononuclear cell (PBMC) culture supernatants, as well as a higher MMP-9/TIMP-3 ratio when compared to the other groups studied. MMP-9 levels positively correlated with proviral load and TNF in OAB-HTLV-infected individuals, and the in vitro neutralization of TNF significantly decreased MMP-9 levels in PBMC culture supernatants. Our findings indicate an association between MMP-9 production and the proinflammatory state associated with HTLV-1 infection, as well as HAM/TSP.

Blood monocytes in maintaining the balance of vascular endothelial injury and repair process in ischemic cardiomyopathy

Highlights. The features of subsets of monocytes in combination with the levels of desquamated endotheliocytes, endothelial damage and regeneration mediators and progenitor cell migration-enhancing factors in patients with coronary heart disease and with/without ischemic cardiomyopathy were analyzed. For the first time it was shown that in patients with ischemic cardiomyopathy, compared with CHD patients without cardiomyopathy, higher desquamation of the endothelium is associated with a deficiency of non-classical monocytes and reduced migration of progenitor endothelial cells (VEGFR2+-monocytes) with regenerative potential across the bone marrow due to a deficiency of the HIF-1α mediator in the blood.Background. The development of ischemic cardiomyopathy (ICM) is an understudied process, and one of its elements may be insufficient regeneration of blood vessels due to an imbalance of subsets of monocytes in the blood.Aim. To assess subsets of monocytes and desquamated endothelial cells in combination with endothelial damage and regeneration mediators in the blood of patients with coronary heart disease (CHD) and with/without ICM.Methods. The study included 30 patients with ICM, 22 patients with coronary heart disease without cardiomyopathy aged 55–69 years, and 18 healthy donors. In whole blood, the populations of CD45–CD146+ desquamated endothelial cells and progenitor endothelial cells related to CD14+VEGFR2+ monocytes, intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes were assessed by flow cytometry using the appropriate monoclonal antibodies (BD Biosciens, USA). In blood plasma, the levels of hypoxia-inducible factor HIF-1α, monocyte chemoattractant protein MCP-1 and matrix metalloproteinase MMP-9 were assessed by enzyme immunoassay. The results of the analysis were considered significant at p&lt;0.05.Results. The number of progenitor and desquamated endothelial cells was increased in both groups of patients with coronary artery disease. At the same time, in patients with ICM, the number of progenitor endothelial cells did not reach the number noted in patients with CHD without cardiomyopathy, while the number of desquamated endothelial cells reached the number noted in CHD patients without cardiomyopathy. There was a deficiency of non-classical monocytes and HIF-1α in the blood of patients with ICM, and an excess of intermediate monocytes and MCP-1 was observed in CHD patients without cardiomyopathy. The concentration of MMP-9 in patients with CHD corresponded to the norm, regardless of the presence of ICM.Conclusion. In ICM, in contrast to CHD without cardiomyopathy, vascular damage is associated with a deficiency of nonclassical monocytes and reduced endothelial repair due to insufficient migration of progenitor endothelial cells across the bone marrow due to HIF-1α deficiency in the blood.

Matrix metalloproteinases in the oral fluid as a characteristic of inflammatory-destructive process in periodontal tissues

The study of the imbalance between the activity of matrix metalloproteinases and their regulation markers in the oral fluid of patients with generalized periodontitis is necessary for creation of effective methods for early diagnosis and preventive treatment of the disease. The aim of the research was to examine the oral fluid of persons with healthy periodontal tissues, patients with chronic diffuse gingivitis and generalized periodontitis for concentrations of matrix metalloproteinases and their inhibitor, anti- and pro-inflammatory cytokines, markers of bone metabolism and to compare obtained results. 90 persons aged 32-45 years were examined, including 30 persons with intact periodontal tissues, 30 patients with chronic diffuse catarrhal gingivitis and generalized periodontitis of the initial degree and 30 ones with chronic generalized periodontitis of I-II degrees. Periodontal status was assessed using clinical indices and bone mineral density according to computed tomography data. The method of enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of matrix metalloproteinases MMP-2, MMP-3, MMP-8, MMP-9, MMP-13, tissue inhibitor of metalloproteinases TIMP-1, interleukins-1β, -6 and -4, bone metabolism markers – tartrate-resistant acidic phosphatase and bone alkaline phosphatase, osteocalcin in the oral fluid. The initiation of the inflammatory-destructive process in the periodontal tissues was characterized by an increase levels of MMP and pro-inflammatory IL-1β and IL-6 (р&lt;0.05), a decrease in the concentration of TIMP-1 (р&gt;0.05) and anti-inflammatory IL-4 (р&lt;0.05), against the background of the absence of dynamics of bone metabolism markers in the oral fluid. The progression of the process at the І-II degrees of periodontitis was accompanied by a further increase in the concentration of pro-inflammatory interleukins, an increase in the activity of tartrate-resistant acid phosphatase and a decrease in bone alkaline phosphatase and osteocalcin (р&lt;0.05) in the oral fluid, while the content of MMP did not change (р&gt;0.05). The expression of MMP is important for the preventive diagnosis of generalized periodontitis, but it is not indicative for determining the severity of the disease. The imbalance of MMP and TIMP-1 in the early stages of the pathological process indicates the greatest expediency of using MMP inhibitors in the treatment of patients with gingivitis and periodontitis of the initial degree.

Matrix Metalloproteinases and Stress Hormones in Lung Cancer Progression.

Several matrix metalloproteinases (MMPs) and psychological stress are associated with poor cancer prognosis. The current work goal was to determine MMPs' and stress hormones' blood concentrations from lung adenocarcinoma (LAC) patients. Patients were divided into the following groups: tobacco smokers (TS), wood smoke-exposed (W), passive smokers (PS), TS exposed to wood smoke (TW), and patients with no recognizable risk factor (N). MMPs, tissue inhibitors of metalloproteinases (TIMPs), adrenaline, noradrenaline, and cortisol blood concentrations were measured by ELISA. Zymography and Western blot assays were performed to determine MMP-2 and MMP-9 active and latent forms. MMP-2, MMP-3, MMP-9, and TIMP-1 blood concentrations, and MMP-9 gelatinase activity were augmented, while MMP-12, MMP-14, and TIMP-2 were diminished in LAC patients. Cortisol was increased in LAC samples. Adrenaline concentrations were higher in W, TS, and TW, and noradrenaline was increased in W and N groups. Positive correlations were observed among cortisol and TIMP-1 (rs = 0.392) and TIMP-2 (rs = 0.409) in the W group and between noradrenaline and MMP-2 (rs = 0.391) in the N group. MMPs' blood concentration increments can be considered as lung cancer progression markers. Although stress hormones were also augmented, only weak correlations were observed between them and MMPs and TIMPs.

DYNAMICS OF MMP8 AND OSTEOPONTIN CONTENT IN ORAL LIQUID OF PATIENTS WITH ORAL DISEASES IN THE PRESENCE OF ONCOPATHOLOGY

According to WHO, breast cancer is one of the most common forms of cancer in women. In 2020, 2.3 million women were diagnosed with breast cancer and 685,000 deaths from the disease were reported worldwide. This research aims to study the dynamics of the concentration of MMP8, osteopontin, and Ca2+ ions, as well as the pH level in patients with breast cancer during chemotherapy and specific dental treatment. Materials and methods. The study involved 60 patients, both men and women. All respondents were divided into groups by their oncological diseases: group 1 consisted of 20 patients with stage II and III breast cancer after chemotherapy, without prior dental treatment, group 2 comprised 20 patients with breast cancer after chemotherapy, with previous dental treatment, the control group included 20 people without cancer and dental pathology. Results and discussion. Dental diseases in patients of both groups were manifested by significant changes in bone metabolism, which was accompanied with sharp rise of MMP8 concentration in oral fluid during reducing osteopontin concentration. It is worth noting that the above pathobiochemical changes occurred against the background of a fall in the Ca2+ ion content and a pH shift towards the acidic side. The increase in Ca2+ is associated with a decrease in MMP8 level and the elevation in pH and osteoponine. In turn, the pH has medium power feedback with MMP8 and a direct relationship of medium force with osteoponin. MMP8 and osteopontin are associated with strong feedback, that is, an increase in the level of one of them can be displayed about reducing osteopontin. Conclusion. This study has established a statistically significant increase in MMP 8 against the background of the reducing concentration of osteoponitis. Pathobiochemical changes in bone tissue were found against the background of significant loss of Ca2+ ions and pH. Dental treatment for this category of patients has led to the improvement in the concentration of these markers. The data obtained justifies the necessity of their use as diagnostic markers and laboratory screening of the effectiveness of dental treatment in patients of this category.

Comprehensive characterization of the postoperative pericardial inflammatory response: Potential implications for clinical outcomes

ObjectiveThere is a paucity of data on the inflammatory response that takes place in the pericardial space after cardiac surgery. This study provides a comprehensive assessment of the local postoperative inflammatory response. MethodsForty-three patients underwent cardiotomy, where native pericardial fluid was aspirated and compared with postoperative pericardial effluent collected at 4, 24, and 48 hours' postcardiopulmonary bypass. Flow cytometry was used to define the levels and proportions of specific immune cells. Samples were also probed for concentrations of inflammatory cytokines, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs). ResultsPreoperatively, the pericardial space mainly contains macrophages and T cells. However, the postsurgical pericardial space was populated predominately by neutrophils, which constituted almost 80% of immune cells present, and peaked at 24 hours. When surgical approaches were compared, minimally invasive surgery was associated with fewer neutrophils in the pericardial space at 4 hours' postsurgery. Analysis of the intrapericardial concentrations of inflammatory mediators showed interleukin-6, MMP-9, and TIMP-1 to be highest postsurgery. Over time, MMP-9 concentrations decreased significantly, whereas TIMP-1 levels increased, resulting in a significant reduction of the ratio of MMP:TIMP after surgery, suggesting that active inflammatory processes may influence extracellular matrix remodeling. ConclusionsThese results show that cardiac surgery elicits profound alterations in the immune cell profile in the pericardial space. Defining the cellular and molecular mediators that drive pericardial-specific postoperative inflammatory processes may allow for targeted therapies to reduce immune-mediated complications.

A Subset of Secreted Proteins in Ascites Can Predict Platinum-Free Interval in Ovarian Cancer.

Simple SummaryIdentifying proteins that correlate with better or worse outcomes may help to identify new treatment approaches for advanced high-grade serous ovarian cancer. Here, we utilize a machine learning technique to correlate the levels of 58 secreted proteins in tumor ascites with the time to disease recurrence after chemotherapy, which is known clinically as the platinum-free interval. We identify several candidate proteins correlated to shorter or longer platinum-free intervals and describe model analysis methods that may be useful for other studies aiming to identify factors impacting patient outcomes. Future validation of these factors in a prospective cohort would confirm their clinical utility, whereas a study of the mechanisms that they impact may identify new therapies.The time between the last cycle of chemotherapy and recurrence, the platinum-free interval (PFI), predicts overall survival in high-grade serous ovarian cancer (HGSOC). To identify secreted proteins associated with a shorter PFI, we utilized machine learning to predict the PFI from ascites composition. Ascites from stage III/IV HGSOC patients treated with neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS) were screened for secreted proteins and Lasso regression models were built to predict the PFI. Through regularization techniques, the number of analytes used in each model was reduced; to minimize overfitting, we utilized an analysis of model robustness. This resulted in models with 26 analytes and a root-mean-square error (RMSE) of 19 days for the NACT cohort and 16 analytes and an RMSE of 7 days for the PDS cohort. High concentrations of MMP-2 and EMMPRIN correlated with a shorter PFI in the NACT patients, whereas high concentrations of uPA Urokinase and MMP-3 correlated with a shorter PFI in PDS patients. Our results suggest that the analysis of ascites may be useful for outcome prediction and identified factors in the tumor microenvironment that may lead to worse outcomes. Our approach to tuning for model stability, rather than only model accuracy, may be applicable to other biomarker discovery tasks.

Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction In Patients With Resistant Hypertension and Type 2 Diabetes Mellitus.

Aim To study the incidence and clinical and pathophysiological features of diastolic dysfunction (DD) and chronic heart failure with preserved ejection fraction (HFpEF) in patients with resistant arterial hypertension (RAH) associated with type 2 diabetes mellitus (DM).Material and methods A cross-sectional study that included 36 patients with RAH associated with type 2 DM (mean age, 61.4±6.4 years; 14 men) was performed. Measurement of office and 24-h blood pressure (BP), standard echocardiography with assessment of diastolic function (DF) and ventricular-arterial coupling, doppler ultrasound imaging of renal blood flow, and laboratory tests (blood glucose, glycated hemoglobin, blood creatinine, tumor necrosis factor α (TNF-α), brain natriuretic peptide (BNP), type 2 and type 9 matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of MMP 1 (TIMP-1), 24-h urine protein test, and 24-h urine volume test were performed for all patients. HFpEF was diagnosed according to criteria of the American Society of Echocardiography and the European Society of Cardiology 2019, and the Russian Clinical Guidelines on Diagnosis and Treatment of CHF 2017 and 2020.Results All patients had DD. Incidence of HFpEF detection according to the Russian Guidelines 2017 was 100%; according to the Russian Guidelines 2020, that included a required increase in BNP, and according to the criteria of the European Guidelines 2019, this incidence was 89 %. In 55.6 % of patients, DD corresponded to grade 2 (pseudonormal type). According to the correlation analysis, the DF impairment was associated with increases in pulse BP, myocardial mass, arterial and left ventricular elastance (arterial wall and left ventricular elasticity), basal glycemia and DM duration, MMP-2 level, proteinuria, blood creatinine, renal vascular resistance, and also with decreases in 24-h urine volume, MMP-9, TIMP-1, and TIMP-1/MMP-2. Significance of the relations of mean E / e' ratio with nighttime pulse BP, MMP-9, and 24-h urine volume were confirmed by results of multiple linear regression analysis. Increased myocardial and vascular wall stiffness, concentrations of MMP-2 and TNF-α and reduced 24-h urine volume were associated with progressive impairment of DF.Conclusion The combination of RAH and DM-2 is characterized by an extremely high incidence of DD that determines a great prevalence of HFpEF. The development and progression of DD in such patients are closely related with a complex of metabolic, proinflammatory and profibrotic biomarkers, increased vascular wall stiffness, pronounced left ventricular hypertrophy, and with structural and functional alterations in kidneys.

MMP-9 Levels in the Gingival Crevicular Fluid of Chilean Rosacea Patients.

Rosacea is a chronic inflammatory skin disease whose prevalence rates remain unknown in Chile. Laboratory benchmark testing for this disease is not useful, therefore, we aimed to evaluate the gingival crevicular fluid (GCF) levels of extracellular metalloproteinases (MMP)-2 and MMP-9 as novel rosacea biomarkers. We designed a cross-sectional study with a control group. Participants were systemically healthy adults (n = 20) and persons with rosacea (n = 18). We performed a periodontal evaluation and collected gingival crevicular fluid to measure MMP-2 and MMP-9 levels. Analysis showed mean and standard deviation of MMP-9 concentrations in the GCF for patients with rosacea was 764.52 ± 569.83 pg/mL; for healthy patients, it was 260.69 ± 170.43 pg/mL (p < 0.05). The diagnosis of rosacea was responsible for the levels of MMP-9 in the GCF (p < 0.05), as opposed to periodontitis, smoking, and age (p > 0.05). The Area under ROC for MMP-9 was 0.869 (95%, C.I: 0.719–0.956), with a sensitivity of 72.22% and specificity of 81.58% for the diagnosis of rosacea. We conclude that the quantification of MMP-9 in the GCF could be used as a biomarker of rosacea. Also, rosacea was responsible for increasing the levels of MMP-9 in the GCF independent of periodontal status.