Matrix metalloproteinases (MMPs) play an important role in central nervous system infections. We analysed the levels of 8 different MMPs in the cerebrospinal fluid (CSF) of 89 adult patients infected with tick-borne encephalitis (TBE) virus and compared them with the levels in a control group. MMP-9 was the only MMP that showed significantly increased CSF levels in TBE patients. Serum MMP-9 levels were subsequently measured in 101 adult TBE patients at various time points during the neurological phase of TBE and at follow-up. In addition, serum MMP-9 was analysed in 37 paediatric TBE patients. Compared with control levels, both paediatric and adult TBE patients had significantly elevated serum MMP-9 levels. In most adult patients, serum MMP-9 levels peaked at hospital admission, with higher serum MMP-9 levels observed in patients with encephalitis than in patients with meningitis. Elevated serum MMP-9 levels were observed throughout hospitalisation but decreased to normal levels at follow-up. Serum MMP-9 levels correlated with clinical course, especially in patients heterozygous for the single-nucleotide polymorphism rs17576 (A/G; Gln279Arg) in the MMP9 gene. The results highlight the importance of MMP-9 in the pathogenesis of TBE and suggest that serum MMP-9 may serve as a promising bioindicator of TBE in both paediatric and adult TBE patients.
- MeSH
- biologické markery MeSH
- dítě MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus MeSH
- klíšťová encefalitida * diagnóza mozkomíšní mok MeSH
- lidé MeSH
- matrixová metaloproteinasa 9 genetika MeSH
- viry klíšťové encefalitidy * genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Tumor necrosis factor-alpha (TNF-α) agonists revolutionized therapeutic algorithms in inflammatory bowel disease (IBD) management. However, approximately every third IBD patient does not respond to this therapy in the long term, which delays efficient control of the intestinal inflammation. METHODS: We analyzed the power of serum biomarkers to predict the failure of anti-TNF-α. We collected serum of 38 IBD patients at therapy prescription and 38 weeks later and analyzed them with relation to therapy response (no-, partial-, and full response). We used enzyme-linked immunosorbent assay to quantify 16 biomarkers related to gut barrier (intestinal fatty acid-binding protein, liver fatty acid-binding protein, trefoil factor 3, and interleukin (IL)-33), microbial translocation, immune system regulation (TNF-α, CD14, lipopolysaccharide-binding protein, mannan-binding lectin, IL-18, transforming growth factor-β1 (TGF-β1), osteoprotegerin (OPG), insulin-like growth factor 2 (IGF-2), endocrine-gland-derived vascular endothelial growth factor), and matrix metalloproteinase system (MMP-9, MMP-14, and tissue inhibitors of metalloproteinase-1). RESULTS: We found that future full-responders have different biomarker profiles than non-responders, while partial-responders cannot be distinguished from either group. When future non-responders were compared to responders, their baseline contained significantly more TGF-β1, less CD14, and increased level of MMP-9, and concentration of these factors could predict non-responders with high accuracy (AUC = 0.938). Interestingly, during the 38 weeks, levels of MMP-9 decreased in all patients, irrespective of the outcome, while OPG, IGF-2, and TGF-β1 were higher in non-responders compared to full-responders both at the beginning and the end of the treatment. CONCLUSIONS: The TGF-β1 and CD14 can distinguish non-responders from responders. The changes in biomarker dynamics during the therapy suggest that growth factors (such as OPG, IGF-2, and TGF-β) are not markedly influenced by the treatment and that anti-TNF-α therapy decreases MMP-9 without influencing the treatment outcome.
Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood samples collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (MMP9) was found in five of the top 10 upregulated pathways, indicating its potential as therapeutic target against COVID-19. In summary, our data demonstrates aberrant activation of endocrine signaling in severe COVID-19, and its implication in immune and metabolic dysfunction.
Hypoxia can cause basement membrane (BM) degradation in tissues. Matrix metalloproteinase 9 (MMP-9) is involved in various human cancers as well as BM degradation by downregulating type IV collagen (COL4). This study investigated the role of MMP-9 in hypoxia-mediated BM degradation in rat bone marrow based on its regulation of collagen type IV alpha 1 chain (COL4A1). Eighty male rats were randomly divided into four groups based on exposure to hypoxic conditions at a simulated altitude of 7,000 m, control (normoxia) and 3, 7, and 10 days of hypoxia exposure. BM degradation in bone marrow was determined by transmission electron microscopy. MMP-9 levels were assessed by western blot and real-time PCR, and COL4A1 levels were assessed by western blot and immunohistochemistry. Microvessels BMs in bone marrow exposed to acute hypoxia were observed by electron microscopy. MMP-9 expression increased, COL4A1 protein expression decreased, and BM degradation occurred in the 10-, 7-, and 3-day hypoxia groups compared with that in the control group (all P < 0.05). Hypoxia increased MMP-9 levels, which in turn downregulated COL4A1, thereby increasing BM degradation. MMP-9 upregulation significantly promoted BM degradation and COL4A1 downregulation. Our results suggest that MMP-9 is related to acute hypoxia-induced BM degradation in bone marrow by regulating COL4A1.
- MeSH
- bazální membrána * metabolismus MeSH
- hypoxie metabolismus MeSH
- kolagen typu IV * metabolismus MeSH
- krysa rodu rattus MeSH
- matrixová metaloproteinasa 9 * metabolismus MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The preocular tear film is critically important for maintaining healthy ocular surface. In lagophthalmos, increased evaporation and tear film instability can occur. The level of tear matrix metalloproteinase 9 (MMP-9) is considered as a possible marker of ocular surface damage and inflammation. The aim of this study was to evaluate the possible usefulness of measuring tear film levels of MMP-9 in patients with lagophthalmos. Sixteen adult patients with unilateral lagophthalmos due to cerebellopontine angle mass surgery were included. Basic clinical examination including tear film osmolarity, degree of lagophthalmos, ocular surface sensitivity testing, corneal fluorescein staining, and tear break-up time (TBUT) were performed. Furthermore, tear MMP-9 quantification was performed and the values from lagophthalmic and contralateral healthy eye were compared. Possible correlations between tear MMP-9 levels and other parameters were analyzed. The Oxford score was higher in lagophthalmic eyes in comparison to healthy eyes. TBUT and corneal sensitivity were lower in lagophthalmic eyes. There was no difference in osmolarity between the two groups. Tear MMP-9 values were higher in lagophthalmic eyes. A higher MMP-9 value was associated with an increase in ocular surface fluorescein staining and a decrease of TBUT in lagophthalmic eyes. Tear MMP-9 may be used for monitoring ocular surface damage, contribute to early detection of inflammation progression and facilitate treatment adjustments.
- MeSH
- dospělí MeSH
- fluorescein MeSH
- lidé MeSH
- matrixová metaloproteinasa 9 MeSH
- nemoci očních víček * MeSH
- osmolární koncentrace MeSH
- poranění oka * MeSH
- slzy MeSH
- syndromy suchého oka * diagnóza MeSH
- zánět MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Aortic dissection (AD) caused by the tear in the aortic wall threatens aorta, causing severe chest pain, syncope and even death. Fortunately, development of genetic technology provides promising approaches for AD treatment. To analyze impacts of miR-15a-5p on modulating cell viability and migratory ability of vascular smooth muscle cells (VSMCs). Ang II (0, 0.05 and 0.1 microM) treatment were applied for inducing inflammatory reactions of VSMCs. RNA expressions of miR-15a-5p with Bcl-2 was examined using RT-qPCR. CCK-8 and transwell evaluated cell viability and migratory ability, respectively. The binding about miR-15a-5p with Bcl-2 were detected by luciferase reporter assay. Western blot detected protein expressions of Bcl-2, MCP-1 and MMP-9. Ang II treatment not only accelerated VSMCs viability and migratory abilities, but also upregulated MCP-1 and MMP-9 protein expressions. MiR-15a-5p was detected to be promoted by Ang II. However, miR-15a-5p inhibitor decreased VSMC cell viability and migratory ability and suppressed protein expressions of MCP-1 and MMP-9. Bcl-2 was targeted and downregulated by miR-15a-5p. Nevertheless, high VSMC cell viability and migration caused by miR-15a-5p overexpression were hindered with overexpressed Bcl-2. MiR-15a-5p mimics also elevated MCP-1 and MMP-9 protein expressions, which were inhibited by Bcl-2 upregulation.
Mangiferin is a glycosylated xanthone widely distributed in nature, which exhibits wide pharmacological activities, highlighting its anti-cancer properties. Mangiferin interferes with inflammation, lipid, and calcium signaling, which selectively inhibits multiple NFkB target genes as interleukin-6, tumor necrosis factor, plasminogen, and matrix metalloproteinase, among others. In this work, the interactions of this polyphenol with MMP-9 and NF-κβ are characterized by using computational chemistry methods. The results show MMP-9 inhibition by mangiferina is characterized for the interact with the catalytic Zn atom through a penta-coordinate structure. It is also demonstrated through a strong charge transfer established between mangiferin and Zn in the QM/MM study. Concerning the mangiferin/NF-κβ system, the 92.3% of interactions between p50 sub-unity and DNA are maintained with a binding energy of - 8.04 kcal/mol. These findings indicate that mangiferin blocks the p50-p65/DNA interaction resulting in the loss of the functions of this hetero-dimeric member and suggesting inhibition of the cancer progression. Experimental results concerning the anti-cancer properties of mangiferin show that this natural compound can inhibit selectively MMP-9 and NF-ƙβ. Although the anti-tumor properties of mangiferin are well defined, its molecular mechanisms of actions are not described. In this work, a computational study is carried out to characterize the interactions of mangiferin with these molecular targets. The results obtained corroborate the anti-proliferative and anti-apoptotic activity of mangiferin and provide a depiction of its mechanisms of action.
Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients. Last, we explored the correlation between MMP9 levels and hippocampal volumes in patients and healthy individuals separately. Patients displayed higher MMP9 plasma levels than healthy individuals (F(1, 60) = 21.19, p < 0.0001). MMP9 levels correlated with negative symptoms in patients (R = 0.39, p = 0.035), but not with medication, duration of illness, or the number of episodes. Further, patients had smaller left (F(1,59) = 9.12, p = 0.0040) and right (F(1,59) = 6.49, p = 0.013) hippocampal volumes. Finally, left (R = -0.39, p = 0.034) and right (R = -0.37, p = 0.046) hippocampal volumes correlated negatively with MMP9 plasma levels in patients. We observe higher MMP9 plasma levels in SCZ, associated with lower hippocampal volumes, suggesting involvement of MMP9 in the pathology of SCZ. Future studies are needed to investigate how MMP9 influences the pathology of SCZ over the lifespan, whether the observed associations are specific for schizophrenia, and if a therapeutic modulation of MMP9 promotes neuroprotective effects in SCZ.
- MeSH
- dospělí MeSH
- hipokampus diagnostické zobrazování patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- matrixová metaloproteinasa 9 * terapeutické užití MeSH
- schizofrenie * farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Úvod: Preeklampsie je onemocnění, které ohrožuje na životě matku I plod. Na celém světě je každý rok diagnostikováno u 10 milionů žen, což odpovídá 3–8 % všech těhotenství. V současné době nemá preeklampsie prokázanou účinnou léčbu. To zdůrazňuje potřebu předpovědi této komplikace. Tato prospektivní studie se provádí za účelem stanovení, zda mají matrixové metaloproteinázy-2 a -9 prognostický význam jako časné markery preeklampsie. Materiály a metody: Hladiny matrixových metaloproteináz-2 a -9 byly hodnoceny u 72 pacientek. U 34 z nich se následně v průběhu těhotenství vyvinula preeklampsie (u 20 pacientek mírná forma, u 14 pacientek těžká forma). Tyto pacientky představovaly základní skupinu. Kontrolní skupinu tvořilo 38 pacientek. Výsledky: U těhotných žen, u nichž se následně vyvinula preeklampsie, byla hladina matrixové metaloproteinázy-2 v 11.–13. týdnu těhotenství 155 ± 73,4 ng/ml a byla významně vyšší než úroveň u těhotných žen bez hypertenzních poruch (75,0 ± 32,8 ng/ml). Prováděná studie prokazuje významně nižší koncentraci matrixové metaloproteinázy 9 u těhotných žen s preeklampsií v porovnání s kontrolní skupinou (749 ± 296 ng/ml vs. 1 667 ± 552 ng/ml; p < 0,001). Provedený výzkum ukazuje, že v prvním trimestru byla mezní hodnota matrixové metaloproteinázy-2 pro predikci rozvoje preeklampsie ≥ 102 ng/ml (senzitivita 88,24 % a specificita 82,76 %). V případě matrixové metaloproteinázy-9 předpovídala v prvním trimestru rozvoj preeklampsie hladina ≤ 980 ng/ml se senzitivitou 85,29 % a specificitou 84,48 %. Závěr: Studie stanovila mezní hodnoty matrixových metaloproteináz-2 a -9 v prvním trimestru pro předpověď rozvoje preeklampsie.
Introduction: Preeclampsia is a life-threatening condition for the mother and foetus. Globally, it is diagnosed in 10 mil. women every year, which accounts for 3% to 8% of all pregnancies. Currently there is no proven effective treatment for preeclampsia. The aforesaid text actualises the issue of predicting this complication. To determine the prognostic significance of matrix metalloproteinases-2 and -9 levels as early markers of preeclampsia, the present prospective study was conducted. Materials and methods: The levels of matrix metalloproteinases-2 and -9 were assessed in 72 patients. Thirty-four of them subsequently developed preeclampsia during pregnancy (20 patients with moderate preeclampsia, 14 patients with severe preeclampsia), and constituted the basic group; 38 patients made up the control group. Results: In pregnant women with the subsequent development of preeclampsia, the level of matrix metalloproteinase-2 at 11–13 weeks of gestation was 155 ± 73.4 ng/mL and significantly exceeded its level in pregnant women without hypertensive disorders – 75.0 ± 32.8 ng/mL. The study conducted demonstrates a significantly lower concentration of matrix metalloproteinase-9 in pregnant women with preeclampsia compared to the control – 749 ± 296 ng/mL and 1,667 ± 552 ng/mL (P < 0.001). The performed research figures that in the first trimester, the cut-off value of matrix metalloproteinase-2 for predicting the development of preeclampsia is ≥ 102 ng/mL (sensitivity 88.24% and specificity 82.76%). For matrix metalloproteinase-9, a level of ≤ 980 ng/mL in the first trimester predicts the development of preeclampsia with a sensitivity of 85.29% and a specificity of 84.48%. Conclusion: The study established the cut-off values of matrix metalloproteinases-2 and -9 for predicting the development of preeclampsia in the first trimester.
Matrix metalloproteinases (MMPs) are associated with the alteration of extracellular matrix. The purpose of this study was to investigate how the levels of matrix metalloproteinases and their inhibitors - TIMPs are influenced by the presence of inguinal hernia as well as by its surgical treatment. The studied group consisted of 25 patients with inguinal hernia and 21 healthy controls for comparison. Two blood samples - before and after the treatment were collected from patients. Serum concentrations of MMPs and TIMPs were analysed by multiplex immunoassays. There was a difference in circulating levels of MMPs in patients before the surgery compared to healthy controls - the concentrations of MMP-2 and MMP-9 were significantly lower (p=0.026, p=0.018, respectively). After the surgery, the levels of MMPs, especially MMP-2 (p<0.0001), were significantly decreased in patients compared to the preoperative values, apart from MMP-9. On the contrary, MMP-9 showed significant increase after the surgery (p<0.0001). Circulation levels of TIMP-2 in patients were significantly decreased in comparison with controls (p=0.004), whereas levels of TIMP-1 were similar to controls. Both tested metalloproteinase inhibitors showed a significant decrease in detected levels (TIMP-1 p=0.0004; TIMP-2 p<0.0001) after the procedure compared to the preoperative values. The levels of MMPs, especially MMP-2 and MMP-9, and their inhibitors TIMP-1 and TIMP-2 are involved by the presence of inguinal hernia as well as are influenced by the surgery.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- inguinální hernie krev enzymologie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 2 krev MeSH
- matrixová metaloproteinasa 9 krev MeSH
- operace kýly * MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- tkáňový inhibitor metaloproteinasy 1 krev MeSH
- tkáňový inhibitor metaloproteinasy 2 krev MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
