Matrix Metalloproteinase-9 Concentrations Research Articles

Effects of adrenocorticotrophic hormone on the expression of matrix metalloproteinases and their inhibitors in the bovine ovary.

Cattle undergo numerous environmental and management stressors that reduce fertility and affect ovulation. The extracellular matrix of the follicle wall can be altered by matrix metalloproteinases (MMPs), the activities of which are regulated by interleukins and tissue-specific inhibitors of metalloproteinases (TIMPs), especially during ovulation. The aims of the present study were to: (1) evaluate changes in the hormone milieu, the localisation and activity of MMP2 and MMP9 and the localisation of MMP14, TIMP1 and TIMP2 in response to adrenocorticotrophic hormone (ACTH) during the preovulatory period in cows; and (2) determine the direct effects of ACTH on the mRNA expression of MMP2 and MMP9 in the cultured follicle wall of bovine ovaries obtained from an abattoir. 100IU ACTH was administered during pro-oestrus every 12h until ovariectomy, which was performed before ovulation. Cortisol concentrations in the plasma and follicular fluid (FF) of preovulatory follicles were higher in ACTH-treated than control cows. Progesterone presented subluteal concentrations in plasma of ACTH-treated cows (P<0.05). MMP2 immunostaining and activity in ovaries were higher in ACTH-treated than control cows (P<0.05), whereas MMP9 immunostaining was similar between the two groups. However, unlike in control cows, MMP9 activity was absent in the FF of ACTH-treated cows. These results suggest that the administration of ACTH during the preovulatory period in cows could cause changes that culminate in modifications in the content and activation of MMPs and TIMPs in the ovary, which could interfere with the ovulation process.

MicroRNA-33b inhibits liver cancer cell proliferation, migration and invasion via down-regulation of Fli-1 and MMP-2 protein expressions

Purpose: To study the influence of microRNA-33b (miR-33b) on liver cancer cell proliferation, migration and invasiveness, and the mechanism involved. Methods: MicroRNA-33b or Fli-1 overexpression plasmid was transfected into liver cancer (SMMC7721) cells. Cell proliferation, migration, and invasiveness were determined using cell counting kit 8 (CCK-8), scratch test, and Transwell invasion assay, respectively. The amounts of miR-33b and Fli-1 in liver cancer tissues, paracancerous normal tissues, and miR-33b overexpression and control groups were measured using qRT-PCR, while protein concentration of matrix metalloproteinase 2 (MMP-2) was assayed using Western blotting. Results: Fli-1 protein was markedly upregulated in liver cancerous cells, relative to paracancerous normal tissues (p < 0.05). MicroRNA-33b protein expression was also significantly upregulated in miR33b overexpression group, but the corresponding Fli-1 expression was downregulated in miR-33b overexpression group, relative to control (p < 0.05). MicroRNA-33b overexpression significantly and time-dependently inhibited SMMC7721 cell proliferation and migration, but it reduced the degree of apoptosis (p < 0.05). Liver cancer (SMMC7721) cells in miR-33b overexpression group were less invasive than the control group (p < 0.05). Similarly, miR-33b overexpression significantly downregulated MMP-2 protein expression in SMMC7721cells (p < 0.05). Conclusion: Overexpression of miR-33b suppresses the proliferation, migratory and invasive potential of hepatic cancer cells via down-regulation of Fli-1 and MMP-2 protein expression. This finding may be useful in the identification of new liver cancer drugs.

Collagenase-2- (MMP-8) as a Poimt - of- care Biomerker in Periodontal Disease in Patients with or Without Fixed Prosthesis Therapeutic Response to Doxycycline

Periodontal diseases ranges from simple gum inflammation to serious disease that consists in major damage to the soft tissue and bone teeth support. Periodontal diseases affects the marginal and apical periodontium and results from the interaction between bacterial biofilm and the host response. To determine the concentrations of MMP-8, as a disease marker, in saliva in prosthetic and nonprosthetic, aggressive (AP) and chronic (CP) periodontitis, doxycycline treated patients. 40 patients were distributed into 3 groups: 12 diagnosed with aggressive (AgP), 18 with chronic (CP) periodontitis. Each of these groups was subdivided into 2 subgroups with and without fixed prosthesis. 10 patients were in the normal group. Matrix metalloproteinase 8 (MMP-8) was evaluated before and after systemic doxycycline (Dox) treatment. mean MMP-8 value into the control group was 0.57 ng/mL with a standard deviation (STD) of 0,094 ng/mL. Highest MMP-8 value was established for the nonprosthesis AgP subgroup, before Dox treatment. The highest reduction in MMP-8 levels (40.8%) was between nonprosthesis AgP before Dox treatment and the same group after Doxycycline treamtent. MMP-8 saliva levels are lower than GCF levels, mostly through a dilution mechanism as previous studies had shown. Our study revealed that saliva MMP-8 level is relible marker for AgP but not for CP. Doxycycline treatment, in terms of lowering MMP-8 levels is most effective in patients that have AP and are also wearing fixed.

Collagenase-2- (MMP-8) as a Poimt - of- care Biomerker in Periodontal Disease in Patients with or Without Fixed Prosthesis Therapeutic Response to Doxycycline

Periodontal diseases ranges from simple gum inflammation to serious disease that consists in major damage to the soft tissue and bone teeth support. Periodontal diseases affects the marginal and apical periodontium and results from the interaction between bacterial biofilm and the host response. To determine the concentrations of MMP-8, as a disease marker, in saliva in prosthetic and nonprosthetic, aggressive (AP) and chronic (CP) periodontitis, doxycycline treated patients. 40 patients were distributed into 3 groups: 12 diagnosed with aggressive (AgP), 18 with chronic (CP) periodontitis. Each of these groups was subdivided into 2 subgroups with and without fixed prosthesis. 10 patients were in the normal group. Matrix metalloproteinase 8 (MMP-8) was evaluated before and after systemic doxycycline (Dox) treatment. mean MMP-8 value into the control group was 0.57 ng/mL with a standard deviation (STD) of 0,094 ng/mL. Highest MMP-8 value was established for the nonprosthesis AgP subgroup, before Dox treatment. The highest reduction in MMP-8 levels (40.8%) was between nonprosthesis AgP before Dox treatment and the same group after Doxycycline treamtent. MMP-8 saliva levels are lower than GCF levels, mostly through a dilution mechanism as previous studies had shown. Our study revealed that saliva MMP-8 level is relible marker for AgP but not for CP. Doxycycline treatment, in terms of lowering MMP-8 levels is most effective in patients that have AP and are also wearing fixed. Keywords: periodontal disease, fixed prosthesis, biomarker, doxycycline treatment

Serum Resistin, Adenylate Cyclase-Associated Protein 1 Gene Expression, and Carotid Intima-Media Thickness in Patients with End-Stage Renal Disease and Healthy Controls

Background: Human resistin is a proinflammatory cytokine with significant proatherogenic effects which acts through adenylyl cyclase-associated protein 1 (CAP1). Chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients have increased cardiovascular risk and resistin levels. Previous studies indicated resistin significance as a predictor of mortality in CKD. Aims: We sought to investigate plasma resistin levels, peripheral blood mononuclear cell (PBMC) resistin mRNA, and for the first time CAP1 mRNA levels in ESRD patients and healthy controls. We also sought to investigate the relation of resistin and CAP1 to carotid intima media thickness (CIMT), CD36 gene expression, and matrix metalloproteinase 9 (MMP-9) circulating levels in ESRD patients and healthy controls. Methods: This study included 33 patients with ESRD and 27 healthy controls. Resistin and MMP-9 levels were measured by ELISA. Resistin, CAP1, and CD36 PBMC mRNA were measured by quantitative PCR. Results: Our study showed that ESRD patients have significantly higher levels of circulatory resistin compared to healthy controls (p < 0.001), while there was no significant difference in resistin mRNA. A significant upregulation of CAP1 and CD36 was observed in the ESRD group (p < 0.001; p < 0.001). Resistin concentration correlated with CIMT in healthy controls (r = 0.512, p = 0.036), and with MMP-9 concentration in ESRD (r = 0.353, p = 0.044) and healthy controls (r = 0.463, p = 0.026). CAP1 correlated positively with CIMT (r = 0.464, p = 0.008) in ESRD, and with CD36 in healthy controls (r = 0.447, p = 0.022) and ESRD (r = 0.824, p < 0.001). Conclusion: The obtained data suggest that high levels of circulating resistin acting upon cells with an upregulated CAP1 gene could contribute to the increased inflammation and accelerated atherosclerosis seen in CKD patients.

Correlation of axial length and myopic macular degeneration to levels of molecular factors in the aqueous

To elucidate the molecular processes associated with the development of myopic macular degeneration (MMD), we measured the intraocular concentrations of molecular factors in emmetropic and myopic eyes. This is a retrospective clinic-based case-control study that included eyes undergoing routine cataract surgery whereby aqueous humour samples were obtained. We measured the concentrations of pigment epithelium derived factor(PEDF), matrix metalloproteinase 2(MMP-2), tissue inhibitor of metalloproteinase(TIMP-2), vascular endothelial growth factor isoform A(VEGF-A), interleukin 8(IL-8), interleukin 6(IL-6), C-reactive protein(CRP), angiopoietin 2(Ang2), and amphiregulin. 38 eyes (axial length (AL): 22.4–32.4 mm), including 12 highly myopic (HM) eyes (AL ≥ 26.5 mm) without MMD and 12 HM eyes with MMD but without neovascularization were included. Eyes with MMD were found to have significantly lower VEGF-A levels (p = 0.007) and higher MMP-2 levels (p = 0.02) than control eyes after adjusting for age and gender. MMP-2 levels correlated positively (r = 0.58, p = 0.002), while VEGF-A levels correlated negatively with longer axial length (r = −0.75, p < 0.001). Both the concentrations of VEGF-A (P = 0.25) and MMP-2 (P = 0.69) were not significantly associated with MMD after adjusting for AL. These findings suggest that the predominant mechanism underlying the development of non-neovascular MMD may be axial elongation, driven in part by MMP-2 related mechanisms.

ЛАБОРАТОРНО-КЛИНИЧЕСКОЕ ОБОСНОВАНИЕ АТРАВМАТИЧНОСТИ ИСПОЛЬЗОВАНИЯ ИНДИВИДУАЛЬНОГО ФОРМИРОВАТЕЛЯ ДЕСНЫ АВТОРСКОЙ КОНСТРУКЦИИ

Subject. To improve the effectiveness of prosthetics for tooth loss, an abutment is proposed, which is used both as an artificial crown and a gum former, which is especially important for prosthetics in the frontal group of teeth. An analysis was made of the local content of matrix metalloproteinases (MMP) 8 and 9 and their tissue inhibitor (TIMP) and buccal cytology in patients before and after dental implantation surgery using the author's technique and the traditional protocol. &#x0D; Objective ― to evaluate the effectiveness and non-invasiveness of using the author’s abutment design under immediate loading by evaluating oral homeostasis and the level of cell proliferation. &#x0D; Methodology. Three groups of patients were examined: the main of 25 patients from 30 to 60 years old, who used the original technique, comparisons - 40 patients of the same age, where prosthetics and implantation were performed according to the traditional two-stage protocol and a control group of 40 somatically preserved patients of the same age, which do not require dental prosthetics. In all groups, MPP 8, 9, TIMP were studied, and the buccal cytology was also evaluated.&#x0D; Results. The pathogenetic role of disorders of the connective tissue matrix in the development of early complications of dental implantation was revealed. &#x0D; Findings: Laboratory studies and clinical observations of patients of the main group and the comparison group indicate the effectiveness and non-invasiveness of the original methods of prosthetics on implants using an individual abutment with a gingiva shaper.

Serum Matrix Metalloproteinase-9 Is Associated With Depression After Acute Ischemic Stroke.

Matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, might cause cerebral damage after stroke and be involved in the development of depressive symptoms. This study aimed to evaluate the association of serum MMP-9 levels and post-stroke depression (PSD).Methods and Results:Serum MMP-9 levels were determined in 558 acute ischemic stroke patients from 7 hospitals comprising the China Antihypertensive Trial in Acute Ischemic Stroke. We assessed depression status using the 24-item Hamilton Depression Rating Scale and defined PSD as a cutoff score of 8. Logistic regression was performed to estimate the risk of PSD associated with serum MMP-9. Discrimination and reclassification for PSD by MMP-9 were analyzed. A total of 222 (39.8%) stroke patients were categorized as PSD within 3 months. Serum MMP-9 concentrations were higher among PSD patients than those without PSD (658.8 vs. 485.7 ng/mL; P<0.001). The multiple-adjusted odds ratio (95% confidence interval) for the highest MMP-9 quartile compared with the lowest quartile was 4.36 (2.49-7.65) for PSD, and 1 standard deviation higher log-MMP-9 was associated with 68% (37-106%) increased odds of PSD. Adding MMP-9 to the conventional risk factors model substantially improved discrimination and reclassification for PSD (all P<0.05). Elevated serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of PSD, suggesting an important prognostic role of MMP-9 for PSD.

MATRIX METALLOPROTEINASES IN CHILDREN WITH A COMBINED BONE INJURY

There were comprehensively examined 55 children, including 35 children with combined bone injury (average age of 12.6 ± 2.3 years), reference group consisted of 20 apparently healthy children (average age of 11.8 ± 2.7 years) without pathology of the motor system. on the 1-3rd and 30th day after the combined bone injury, changes in the content of matrix metalloproteinases (MMP) and cytokines - transforming growth factor-beta (TGF-β), monocytic chemotactic factor (MCP-1) and macrophage inflammatory protein (MIP-1β) were followed in the dynamics by serum immunoassay determination. It was established that after combined bone injury at the stage of post-traumatic formation of the regenerate by 30th days the serum concentrations of gelatinases (MMP-2, MMP-9) and collagenases (MMP-8) significantly increased, the levels of stromelysins (MMP-3) did not change, and the content of TIMP-1 decreased. Early detection of changes in the blood content of bone biomarkers during the recovery process after a combined trauma in children allows the timely implementing the correction of disturbances and the choice of the optimal individual treatment tactics for a particular patient, taking into account the features of his bone metabolism.

Does metabolic status affect serum levels of BDNF and MMP-9 in patients with schizophrenia?

The purpose of the article: Brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) are involved in the processes of neurogenesis, synaptic plasticity, learning and memory. Growing number of studies shows a relationship between BDNF or MMP-9 and schizophrenia. Also, BDNF and MMP-9 levels may be affected by metabolic parameters, such as obesity or dyslipidemia. Our hypothesis is that alterations of BDNF or MMP-9 levels in schizophrenia might be secondary to metabolic abnormalities, often found among schizophrenia patients. Materials and methods: We have compared BDNF and MMP-9 between patients with schizophrenia (n = 64, age 49 ± 8.2 y) and healthy controls (n = 32, age 51 ± 8.9 y) in the context of cardio-metabolic parameters. Serum levels of BDNF and MMP-9 were measured using ELISA test, body composition parameters were determined using bioelectric impedance analysis. Results and conclusions: Our results showed significantly lowered serum BDNF concentration in the schizophrenia group (schizophrenia: 23.8 ± 7.83 ng/mL, control: 27.69 ± 8.11 ng/mL, p = 0.03). Serum MMP-9 concentration in schizophrenia group did not differ compared with the control group (schizophrenia: 456.8 ± 278.4 ng/mL, control: 341.5 ± 162.4 ng/mL, p = 0.07). After adjusting for age, all anthropometric parameters, body composition and laboratory tests BDNF were still significantly lower in the schizophrenia group. However, MMP-9 became significantly elevated in the schizophrenia group after adjusting for several anthropometric and body composition covariates. Our results confirmed reduced serum BDNF concentration in patients with schizophrenia. Also, this reduction seems to be independent of metabolic abnormalities. On the other hand, our hypothesis that MMP-9 level in schizophrenia is altered due to metabolic abnormalities might be true.

Investigation of Cytokine Changes in Osteoarthritic Knee Joint Tissues in Response to Hyperacute Serum Treatment.

One option to fight joint degradation and inflammation in osteoarthritis is the injection of activated blood products into the synovial space. It has been demonstrated that hyperacute serum is the most proliferative among plasma products, so we investigated how the cytokine milieu of osteoarthritic knee joint reacts to hyperacute serum treatment in vitro. Cartilage, subchondral bone, and synovial membrane explanted from osteoarthritic knees were stimulated by interleukin-1 beta (IL-1β) and the concentration of 39 biomarkers was measured in the co-culture supernatant after hyperacute serum treatment. The IL-1β stimulation triggered a strong inflammatory response and enhanced the concentrations of matrix metalloproteinase 3 and 13 (MMP-3 and MMP-13), while hyperacute serum treatment reduced inflammation by decreasing the concentrations of IL-1β, tumor necrosis factor alpha (TNF-α), interleukin-6 receptor alpha (IL-6Rα), and by increasing the level of interleukin-1 antagonist (IL-1RA) Cell viability increased by day 5 in the presence of hyperacute serum. The level of MMPs-1, 2, and 9 were higher on day 3, but did not increase further until day 5. The concentrations of collagen 1 alpha 1 (COL1A1) and osteonectin were increased and receptor activator of nuclear factor kappa-B ligand (RANKL) was reduced in response to hyperacute serum. We concluded that hyperacute serum treatment induces cell proliferation of osteoarthritic joint tissues and affects the cytokine milieu towards a less inflamed state.

Acceleration of wound healing activity with syringic acid in streptozotocin induced diabetic rats

Impaired wound healing is a serious concern of uncontrolled hyperglycemia that can lead to gangrene, and even death. There is an urgent need to look for better alternative therapy because of the undesirable side effects of currently available synthetic drugs in the market. Syringic acid (SA) is a natural phenolic compound abundantly available in edible fruits and plants. In this study, wound healing activities of 2.5% and 5.0% SA were evaluated in type 2 diabetic rats using incisional wound model. SA-treated diabetic wounds showed faster rate of wound closure and epithelization with enhanced contents of hydroxyproline and protein compared to diabetic wounds. SA effectively prevents alterations in blood glucose levels, serum insulin and dyslipidemia in diabetic wound rats. The SA-treated diabetic wounds after 14 days of treatment demonstrated inhibition of pro-inflammatory response (NF-κB p65, TNF-α, IL-1β, IL-8 and IL-2) with improvement in anti-inflammatory response (IL-10), inhibited the elevated oxidative stress and decreased the concentrations of matrix metalloproteinases (MMP-2, −8 and −9) and increased the concentrations of TIMP-1 & TIMP- 2. Furthermore, the diabetic wounds were presented with an increase in expression of CD 31 and 68, growth factors (TGF-β1, collagen-I and α-SMA and VEGF) with significant improvement in collagen deposition, re-epithelialization and complete skin structure as revealed by histological analysis after treatment of diabetic wounds with SA for 14 days. Hence, the results of this study designate that SA significantly improves wound healing in diabetic rats and could be used as a potential therapy for treatment of diabetic wounds.

Changes in the Matrix Metalloproteinase 9 Point-of-Care Test Positivity According to MMP-9 Concentration and Loading Volume.

To measure changes in the matrix metalloproteinase 9 (MMP-9) point-of-care test, InflammaDry (Rapid Pathogen Screening, Inc, Sarasota, FL) positivity, based on ocular surface MMP-9 concentrations and loading volume. Two different MMP-9 products, preform and active, were analyzed using the InflammaDry test, detecting MMP-9 levels of more than 40 ng/mL of both preform and active MMP-9. Preform MMP-9 (Natural human MMP-9 protein; Abcam, Cambridge, UK) was analyzed at different concentrations (50, 100, 500, 1000, and 1500 ng/mL) and loading volumes (5, 10, and 20 μL). Active MMP-9 (Human MMP-9 protein; Novus Biologicals, Littleton, CO) was also analyzed using the InflammaDry test at different concentrations (50 and 100 ng/mL) and loading volumes (10, 20, and 40 μL). Natural human MMP-9 protein (preform) of 50, 100, and 500 ng/mL exhibited negative results for every loading volume. At 1000 ng/mL, the 20 μL volume was positive, whereas the 5 and 10 μL volumes were negative. At 1500 ng/mL, all loading volumes were positive, but the density of positive bands varied depending on the loading volume; larger loading volumes had higher band density. Human MMP-9 protein (active) of 50 ng/mL was negative for every loading volume. In 100 ng/mL, the 20 and 40 μL volumes showed positive results with similar positive band densities. The InflammaDry test had a different detection range depending on MMP-9 formulas; higher concentrations of preform MMP-9 protein were needed to yield positive results. In addition, InflammaDry positivity varied based on the loading volumes. Clinicians should be aware of the possibility of false negatives with low tear volumes despite elevated MMP-9 concentrations.

Adverse Reaction of Dextran Sodium Sulfate-Induced Colitis in a Collagen-Induced Mouse Arthritis Model.

The pathogenic relationship of ulcerative colitis and rheumatoid arthritis is not known. Therefore, we examined dextran sodium sulfate (DSS)-induced colitis separately and in combination with a mouse arthritis model that mimics rheumatoid arthritis and evaluated the deterioration-related factors of each condition. Arthritis was induced in a collagen-induced arthritis mouse model using DBA/1JJmsSlc mice and ulcerative colitis was induced by the administration of drinking water containing 3.0% (w/v) DSS. The arthritis/DSS-treated mice developed worse colitis scores compared to that of the other groups of mice. The arthritis/DSS-treated mice did not demonstrate changes in hind foot volumes or in the concentration of matrix metalloproteinase-3 (MMP-3) in the plasma; however, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α were increased. Our results showed that IL-6 and TNF-α may influence the deterioration effect of colitis in arthritic mice.

Role of Matrix Metalloproteinase-9 in Neonatal Hypoxic-Ischemic Encephalopathy.

BACKGROUND:Neonatal encephalopathy is a heterogeneous syndrome characterised by signs of central nervous system dysfunction in the newborn. Matrix metalloproteinase-9(MMP-9) increases the blood-brain barrier permeability, and their inhibitors can reduce its damage. MMP-9 has been implicated specifically in cerebral ischemia.AIM:To measure serum MMP-9 in neonatal hypoxic-ischemic encephalopathy and evaluate its correlation to the severity of early prediction and treatment.METHODS:its case-control study. The serum concentration of MMP-9 was determined by ELISA in 100 hypoxic neonates and 50 healthy neonates of matched age and sex who served as controls.RESULTS:In our present study the serum MMP-9 level was significantly higher at p = 0.0001 in hypoxic-ischemic full-term newborns (176.7 ± 68.7 ng/ml)as compared to control newborn (69.4 ± 34.85 ng/ml)and it was significantly higher at p = 0.0075 in hypoxic-ischemic preterm newborn (171.2 ± 132.9 ng/ml) when compared to control newborn (72.54 ± 36.74 ng/ml), also MMP-9 was significantly higher at Sarnat stage III at p = 0.0001.CONCLUSION:Serum MMP-9 level was significantly higher in hypoxic-ischemic newborns, and significantly increased with severity, so we suggest that serum MMP-9 level is important for predicting neurological sequel and severity in neonatal encephalopathy.

Postpartum human breast milk levels of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9)/NGAL complex in normal and pregnancies complicated with insulin-dependent gestational diabetes mellitus. A prospective pilot case-control study

Neutrophil gelatinase-associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) are present in a variety of human tissues and extracellular fluids. The aim of this pilot prospective case-control study was to detect NGAL and MMP-9/NGAL complex in human breast milk postpartum in women with normal and pregnancies that developed insulin-depended gestational diabetes mellitus (iGDM). We detected both biomarkers in human breast milk and concentrations were determined at the first day of colostrum secretion and two days after, in 22 normal pregnancies and 13 pregnancies with iGDM. Mean NGAL concentration decreased significantly from the first to the second sample, in both groups. Mean MMP-9/NGAL complex concentration decreased also significantly from the first to the second sample in normal pregnancies. Mean complex concentration was significantly higher in diabetic pregnancies compared to normal ones in the second sample.IMPACT STATEMENTWhat is already known on this subject? There is limited information on the presence of Neutrophil gelatinase-associated lipocalin (NGAL) in human milk and its physiological role.What the results of this study add? It is the first time that MMP-9/NGAL complex is detected in human milk in both normal and pregnancies complicated with insulin-depended gestational diabetes mellitus (iGDM). We confirm the presence of NGAL in colostrum of normal pregnancies and for the first time we detected NGAL in milk of pregnancies with iGDM. Concentrations of NGAL and MMP-9/NGAL complex tend to lessen postpartum in both groups. Pregnancies with iGDM compared to normal ones showed significantly higher concentration of MMP-9/NGAL complex two days after the beginning of lactation.What the implications are of these findings for clinical practice and/or further research? Further studies are necessary to determine the levels of NGAL and MMP-9/NGAL complex in human milk postpartum in normal and pathological pregnancies. Taking into consideration the well-established NGAL’s ability to act as a bacteriostatic agent and its mucosal healing activity in gastrointestinal track, early breastfeeding of neonates is a logical recommendation. Finally, new studies on the actual physiological role of milk NGAL in neonates are necessary.

Antimetastatic effects of calycosin on osteosarcoma and the underlying mechanism.

Osteosarcoma (OS) refers to a malignant tumor with potential invasiveness and metastasis; however, the current chemotherapy of OS is lacking. Thus, the alternative drug for treating OS is urgent to explore. Calycosin (CC) is evidenced in our previous study to play the anti-OS benefits for suppressing cancer cell proliferation. Consequently, further investigation of CC-medicated anti-invasive and metastatic effects against OS is needed. In the current study, the clinical samples of OS patients were collected for biological and staining assays, such as enzyme-linked immunosorbent assay and polymerase chain reaction. Meanwhile, the cell line and tumor-bearing nude mice were employed in assessing antimetastatic effects of CC against OS through biochemical tests and immunoassays. As a result, the OS patients exhibited upregulated neoplastic expressions of matrix metalloproteinase 2 (MMP2) and proliferating cell nuclear antigen (PCNA), cellular mRNAs and proteins of inhibitor of nuclear factor kappa-B alpha (IκBα), and epithelial cell transforming sequence 2 (ECT2). In cell-line study, CC-treated human OS cells exhibited induced cell apoptosis, reduced cell proliferation, and cellular MMP2 and PCNA concentration, inhibited cell migration, lowered expressions of IκBα ECT2 mRNAs, and proteins. In tumor-bearing nude mice study, CC-treated mice resulted in the dose-dependent reductions of tumor weights and intracellular MMP2 contents. As shown in further assays, neoplastic expressions of interleukin 6 protein, IκBα, ECT2 mRNAs, and proteins were downregulated dose-dependently in CC-treated tumor-bearing mice. In conclusion, these investigative findings suggest that CC may play the potential anti-invasive benefits against OS through suppressing metastasis-associated IκBα/ECT2 molecular pathway.

Biological response to peri-implantitis treatment.

To investigate biological markers of peri-implantitis (PIP) in crevicular fluid before and after surgical and antimicrobial therapy. Forty-eight participants (24 healthy implants and 24 PIP) were clinically evaluated, and peri-implant crevicular fluid (PICF) samples were collected at baseline for both groups, and at 3-months after surgical and antimicrobial treatment (ie, n=21 PIP completers). Samples were analyzed for interleukin-1β (IL-1β), matrix metalloproteinase-8 (MMP-8), and macrophage inflammatory protein-1α (MIP-1α) using immunoassay and the results compared between groups. Peri-implantitis sites at baseline demonstrated significantly higher mean periodontal probing depths, percentage bleeding on probing (P≤0.001), and mean IL-1β concentration in PICF compared to healthy implant sites (17.9 vs 1.7pg/μL; P=0.02). Three months after treatment, periodontal probing depths, bleeding on probing, suppuration (P<0.05), and the mean concentration of MMP-8 decreased significantly compared with baseline (12.1 vs 6.7ng/μL, P=0.04). MIP-1α concentrations showed no differences between the groups. Elevated concentrations of IL-1β in PICF were consistent with PIP. A decrease in MMP-8 concentration in PICF at three months after treatment is consistent with a healing biological response.

NSE, S100B and MMP9 Expression Following Reperfusion after Carotid Artery Stenting.

Previous studies have shown that the neuron-specific- enolase (NSE), S100B protein (S100B) and matrix metalloproteinase-9 (MMP9) are specific markers for studying cerebral injury. This study was aimed to demonstrate these biomarkers for their correlation with reperfusion after carotid artery stenting (CAS). In this study, a total of 44 patients who were diagnosed unilateral carotid artery stenosis by digital subtraction angiography (DSA) and underwent CAS, were selected as the operation groups. The patients' blood samples were collected at three different time points: T1, prior to operation; T2, next morning after operation (24 hours); T3, three days after operation (72 hours); All of the patients with the operation received computed tomography perfusion (CTP) at T1 and T3. The second group of 12 patients, who were excluded for carotid artery stenosis by DSA, were assigned to be the control group; Blood samples of these patients were collected at T1. The concentrations of NSE, S100B and MMP9 in serum from patients of both groups were detected by ELISA. All of the operations were implanted in stents successfully without complications. (1) After CAS, rCBF increased while rMTT and rTTP decreased. (2) The concentrations of NSE, S100B and MMP9 in the serum decreased gradually (T1>T2>T3). There was no significant difference between the control group and the operation group at T1 (P>0.05) on their concentrations of NSE, S100B and MMP9 in the serum. When compared among the operation groups, the concentrations of NSE, S100B and MMP9 in the serum at T1 and T3 showed significant difference (P<0.05). (3) Correlation analysis among the operation groups indicated that NSE, S100B, MMP9 and rCBF were positively correlated before operation (r = 0.69, 0.58 and 0.72, respectively, P < 0.05), as well as after operation (r = 0.75, 0.65 and 0.60, respectively, P < 0.05). We concluded that the concentrations of NSE, S100B and MMP9 in serum decreased with the improvement of cerebral reperfusion after CAS. NSE, S100B and MMP9 can be used as laboratory biochemical markers to evaluate the improvement of reperfusion after CAS. The results very well complement the imaging methods, such as CTP.

Predictive Significance of Serum MMP-9 in Papillary Thyroid Carcinoma.

ObjectiveThe incidence of papillary thyroid carcinoma (PTC) is increasing, and there are no reliable serum biomarkers for the diagnosis and prognosis of PTC. This study aimed to assess whether serum matrix metalloproteinase-9 (MMP-9) could serve as an auxiliary diagnostic/prognostic marker for PTC after total and partial thyroidectomy.Material and MethodsPostoperative serum MMP-9 concentrations were measured in 182 male patients with PTC, 86 male patients with benign thyroid nodule (BTN), and 62 male healthy controls (HCs). Multivariate logistic regression and Cox regression were applied to evaluate the correlation between variables. The performance of serum MMP-9 in diagnosing PTC and predicting structural persistent/recurrent disease (SPRD) during 48 months of follow-up after initial surgery was evaluated by receiving operating characteristic curve analysis.ResultsThe median serum MMP-9 concentration in the PTC group (79.45 ng/ml) was significantly higher than those in the BTN group (47.35 ng/ml) and HC group (47.71 ng/ml). The area under the curve (AUC) for predicting PTC from BTN was 0.852 at a cut-off value of 60.59 ng/ml. Serum MMP-9 was negatively correlated with disease-free survival (OR 1.026, P=0.001). Serum MMP-9 exhibited good performance in predicting SPRD at a cutoff value of 99.25 ng/ml with an AUC of 0.818. Advanced TNM stage (OR 31.371, P=0.019) and serum MMP-9 ≥99.25 ng/ml (OR 4.103, P=0.022) were independent risk factors for SPRD.ConclusionsSerum MMP-9 potentially represents a good predictive biomarker for PTC diagnosis and prognosis after thyroidectomy in Chinese male patients for whom radio-imaging indicates suspected PTC.