scholarly journals Diagnostic value of matrix metalloproteinase-2 and high mobility group box 1 in patients with refractory epilepsy

2020 ◽  
Vol 56 (1) ◽  
Author(s):  
Khalid S. Salih ◽  
Farqad B. Hamdan ◽  
Qasim S. Al-Mayah
Keyword(s):  
Roc Curve ◽  
Refractory Epilepsy ◽  
High Mobility ◽  
Serum Levels ◽  
Diagnostic Value ◽  
High Mobility Group ◽  
Matrix Metalloproteinase 2 ◽  
Hmgb1 Level ◽  
Epileptic Patients ◽  
Serum Hmgb1 Level

Abstract Introduction There are large numbers of inflammatory molecules and humoral mediators that can be involved in the epileptogenesis such as cytokines, matrix metalloproteinases (MMP), and high mobility group box-1 (HMGB1). We aimed to evaluate serum levels and the diagnostic value of MMP-2 and HMGB1 in Iraqi patients with epilepsy. Methods One hundred epileptic patients comprised 60 controlled epileptics and 40 refractory patients to treatment with multi antiepileptic drugs (AEDs). Other 50 family-unrelated age- and sex-matched healthy subjects were selected to represent the control group. Serum levels of MMP-2 and HMGB1 were estimated using ELISA. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of these markers when required. Results MMP-2 level was significantly higher in controls than epileptic patients in general (controlled and refractory patients). ROC curve, showed poor diagnostic value of MMP-2 in discriminating epileptics into responsive or refractory to treatment from controls (AUC = 0.679 (95% CI = 0.536-0.823), and AUC = 0.77 (95% CI = 0.637-902), respectively). Serum HMGB1 level in epileptic patients and controls was in close approximation to each other. Conclusions MMP-2 is significantly decreased in patients particularly those with refractory epilepsy (RE); however, it has poor diagnostic value. No difference in the serum HMGB1 level between epileptic patients and controls.

scholarly journals Correlation between Serum Levels of High Mobility Group Box-1 Protein and Pancreatitis: A Meta-Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yan Lin ◽  
Lian-Jie Lin ◽  
Yu Jin ◽  
Yong Cao ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Meta Analysis ◽  
High Mobility ◽  
Serum Levels ◽  
High Mobility Group ◽  
Cochrane Library ◽  
Case Control Studies ◽  
Aberrant Expression ◽  
Hmgb1 Level ◽  
Diagnostic Score ◽  
Standard Mean Difference

Background. Aberrant expression of high mobility group box-1 protein (HMGB1) contributes to the progression of various inflammatory diseases. This meta-analysis focused on the clinical significance of serum HMGB1 levels in pancreatitis patients, with the goal of building a novel diagnostic score model.Method. We conducted a meta-analysis by searching in the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases without any language restrictions. Studies were pooled and standard mean difference (SMD) and its corresponding 95% confidence intervals (95% CIs) were calculated. Version 12.0 STATA software was used for statistical analysis.Results. We performed a final analysis of 841 subjects from 12 clinical case-control studies. The meta-analysis results showed a positive association between serum HMGB1 levels and the progression of pancreatitis. In the subgroup analysis by country, high serum level of HMGB1 may be related to pancreatitis progression in China, Korea, Hungary, and Japan populations (allP<0.05).Conclusion. The present meta-analysis indicated that serum HMGB1 level was statistically elevated in patients with pancreatitis, and thus serum levels of HMGB1 could be determined to be a useful biomarker for pancreatitis patients.

scholarly journals High Mobility Group Box 1: a Novel Host Restriction Factor in Zika Virus Replication

2021 ◽  
Author(s):  
Kim-Ling Chin ◽  
Nurhafiza binti Zainal ◽  
Sing-Sin Sam ◽  
Pouya Hassandarvish ◽  
Rafidah Lani ◽  
...  
Keyword(s):  
Zika Virus ◽  
Severe Disease ◽  
High Mobility ◽  
High Mobility Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Zikv Infection ◽  
Hmgb1 Level ◽  
Antiviral Effects ◽  
Huh7 Cells

Abstract Neonatal microcephaly and adult Guillain-Barré syndrome are severe complications of Zika virus (ZIKV) infection. The robustly induced inflammatory cytokine expressions in ZIKV-infected patients may constitute a hallmark for severe disease. In the present study, the potential role of high mobility group box 1 protein (HMGB1) in ZIKV infection was investigated. HMGB1 protein expression was determined by the enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. HMGB1’s role in ZIKV infection was also explored using treatment with dexamethasone, an immunomodulatory drug. Antiviral effects of dexamethasone treatment on both wild-typed (WT) and HMGB1-knockdown (shHMGB1) Huh7 cells were determined by the focus-forming assay. Results showed that the Huh7 cells were highly susceptible to ZIKV infection. The infection was found to induce HMGB1 nuclear-to-cytoplasmic translocation, resulting in a >99% increase in the cytosolic HMGB1 expression at 72h.p.i. The extracellular HMGB1 level was elevated in a time- and multiplicity of infection (MOI)- dependent manner. Dexamethasone 150 µM treatment of the ZIKV-infected cells reduced HMGB1 extracellular release in a dose-dependent manner, with a maximum reduction of 71 ± 5.84% (p < 0.01). The treatment also reduced virus titers by over 83 ± 0.50% (p < 0.01). The antiviral effects, however, was not observed in the dexamethasone-treated HMGB1-knockdown cells, suggesting the importance of the intracellular HMGB1 in ZIKV infection. Overall, these results suggest that translocation of HMGB1 occurred during ZIKV infection and inhibition of the translocation reduced ZIKV replication. These findings highlight the potential of developing therapeutics against ZIKV infection by affecting the translocation of HMGB1 from the nucleus to the cytoplasm.

Serum levels of high mobility group box 1 correlate with disease severity in recessive dystrophic epidermolysis bullosa

2013 ◽  
Vol 22 (6) ◽  
pp. 433-435 ◽  
Author(s):  
Gabriela Petrof ◽  
Alya Abdul-Wahab ◽  
Laura Proudfoot ◽  
Rashida Pramanik ◽  
Jemima E. Mellerio ◽  
...  
Keyword(s):  
Disease Severity ◽  
Epidermolysis Bullosa ◽  
High Mobility ◽  
Serum Levels ◽  
High Mobility Group ◽  
Dystrophic Epidermolysis Bullosa ◽  
Recessive Dystrophic Epidermolysis Bullosa

Dynamic Defense System Against HMGB1, a Proinflammatory and Lethal Mediator in Severe Infections and Malignancies.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3827-3827
Author(s):  
Takashi Ito ◽  
Kazuhiro Abeyama ◽  
Ko-ichi Kawahara ◽  
Kamal K. Biswas ◽  
Tomonori Uchimura ◽  
...  
Keyword(s):  
Tissue Injury ◽  
High Mobility ◽  
Inflammatory Cells ◽  
Defense System ◽  
Hmgb1 Level ◽  
Beneficial Effects ◽  
Extracellular Milieu ◽  
Severe Infections ◽  
Serum Hmgb1 Level ◽  
Severe Tissue

Abstract High Mobility Group box 1(HMGB1) is an abundant DNA-binding protein that acts as a proinflammatory cytokine when released in the extracellular milieu by necrotic and inflammatory cells. Moreover, an increased HMGB1 in the circulation of septic patients may induce multi-organ failure and lethality. However, very recent observations suggest that the protein also acts as an innate adjuvant, stem cell chemoattractant and growth factor. Thus only systemic and circulatory HMGB1 may induce morbidity and mortality, however, localized HMGB1 may have beneficial effects. Therefore, we serially examined the serum HMGB1 level in patients with various diseases, and also evaluated the significance of the protein. We demonstrate here how HMGB1 is localized and acts as an immune-adjuvant and a repairing factor in damaged tissue. We first established specific ELISA method to measure HMGB1. An increased level of HMGB1 was detected in the serum from patients with sever sepsis, infections, malignancy and so on. However, serum HMGB1 concentrations were fluctuated during the clinical course, and could not be concluded as a lethal mediator as previously reported. Next we investigated the reason of dynamic fluctuations of the protein in the circulation. Based on our findings, we proposed that this fluctuation of HMGB1 concentrations may be mediated by at least following three fashions; 1) proteolytic degradation by plasmin and thrombin, 2) endothelial thrombomodulin(TM) adsorption, and 3) generation of antibody against the protein. We observed that plasmin efficiently degraded HMGB1 into small fragments. However, interestingly the generated fragments of the protein still possess an ability to produce TNFa in macrophages through an undefined pathway. TM binds the protein on its N-terminus lectin-like domain. Binding of HMGB1 to TM resulted in decrement of TM’s cofactor activity to activate protein C by thrombin. HMGB1 bound to TM was gradually degraded by thrombin. These may be a system to localize HMGB1 only in injury sites where TM is down-regulated or disappeared through endothelial-loss. This may exert endothelial defense system against extracellular HMGB1 in severe tissue injury. Another possibility is that the generated antibody against HMGB1 may neutralize the proinflammatory action of the protein. In this context, we found that some of the antibodies against HMGB1 have the characteristics of P-ANCA(perinuclear anti-neutrophil cytoplasmic antibody). This may alter the phenotype of the underlining diseases. In conclusion, we suggest that HMGB1 is not merely a lethal mediator, but a kind of “testament” mediator of cell necrosis or invasive attacks to dendritic cells.

scholarly journals Elevation of High-Mobility Group Protein Box-1 in Serum Correlates with Severity of Acute Intracerebral Hemorrhage

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Yu Zhou ◽  
Kun-Lin Xiong ◽  
Sen Lin ◽  
Qi Zhong ◽  
Feng-Lin Lu ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Inflammatory Diseases ◽  
High Mobility ◽  
Serum Levels ◽  
Underlying Mechanism ◽  
High Mobility Group ◽  
Control Group ◽  
High Mobility Group Protein ◽  
Group Protein ◽  
Acute Intracerebral Hemorrhage

High-mobility group protein box-1 (HMGB1) is a proinflammatory involved in many inflammatory diseases. However, its roles in intracerebral hemorrhage (ICH) remain unknown. The purpose of this study was to examine the correlation between changes in serum levels of HMGB1 following acute ICH and the severity of stroke as well as the underlying mechanism. Changes in serum levels of HMGB1 in 60 consecutive patients with primary hemispheric ICH within 12 hours of onset of symptoms were determined. The correlation of HMGB1 with disease severity, IL-6, and TNF-αwas analyzed. Changes in HMGB1 levels were detected with ELISA and Western blot. Compared with normal controls, patients with ICH had markedly elevated levels of HMGB1, which was significantly correlated with the levels of IL-6 and TNF-α, NIHSS score at the 10th day, and mRS score at 3 months. In comparison with the control group, the levels of HMGB1 in the perihematomal tissue in mice with ICH increased dramatically, peaked at 72 hours, and decreased at 5 days. Meanwhile, heme could stimulate cultured microglia to release large amounts of HMGB1 whereasFe2+/3+ions failed to stimulate HMGB1 production from microglia. Our findings suggest that HMGB1 may play an essential role in the ICH-caused inflammatory injury.

scholarly journals The Protective Effect of Lidocaine on Septic Rats via the Inhibition of High Mobility Group Box 1 Expression and NF-κB Activation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Huan-Liang Wang ◽  
Yan-Qiu Xing ◽  
Ying-Xue Xu ◽  
Fei Rong ◽  
Wei-Fu Lei ◽  
...  
Keyword(s):  
Protective Effect ◽  
Cecal Ligation ◽  
High Mobility ◽  
Inhibitory Effect ◽  
High Mobility Group ◽  
Organ Injury ◽  
Hmgb1 Level ◽  
Multiple Organs ◽  
Hmgb1 Expression ◽  
Local Anesthetic Drug

Lidocaine, a common local anesthetic drug, has anti-inflammatory effects. It has demonstrated a protective effect in mice from septic peritonitis. However, it is unknown whether lidocaine has effects on high mobility group box 1 (HMGB1), a key mediator of inflammation. In this study, we investigated the effect of lidocaine treatment on serum HMGB1 level and HMGB1 expression in liver, lungs, kidneys, and ileum in septic rats induced by cecal ligation and puncture (CLP). We found that acute organ injury induced by CLP was mitigated by lidocaine treatment and organ function was significantly improved. The data also demonstrated that lidocaine treatment raised the survival of septic rats. Furthermore, lidocaine suppressed the level of serum HMGB1, the expression of HMGB1, and the activation of NF-κB p65 in liver, kidneys, lungs, and ileum. Taken together, these results suggest that lidocaine treatment exerts its protective effection on CLP-induced septic rats. The mechanism was relative to the inhibitory effect of lidocaine on the mRNA expression level of HMGB1 in multiple organs, release of HMGB1 to plasma, and activation of NF-κB.

scholarly journals MiR-106B Represents an Innovative Bio-marker in Cholangiocarcinoma Detection

2020 ◽  
Author(s):  
Ning Wang ◽  
Yanni Li ◽  
Yanfang Zheng ◽  
Huoming Chen ◽  
Xiaolong Wen ◽  
...  
Keyword(s):  
Roc Curve ◽  
Clinical Stage ◽  
Serum Levels ◽  
Diagnostic Value ◽  
Diagnostic Biomarker ◽  
Chi Square ◽  
Chi Square Test ◽  
Healthy Control ◽  
Important Regulator ◽  
Polymerase Chain

Abstract Background Cholangiocarcinoma (CCA) is one of the most aggressive malignancies. Late diagnosis may be responsible for the high mortality. MicroRNA-106b (MiR-106b) is accepted as an important regulator in various human malignancies. The current study was aimed to investigate the diagnostic value of miR-106b in CCA. Methods Serum levels of miR-106b in CCA patients and healthy control were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was used to analyze the association of miR-106b with the clinicopathological features. To evaluate the diagnostic value of miR-106b in CCA, the ROC curve was constructed. Results The expression of miR-106b was significantly increased in CCA samples compared with the healthy controls (P < 0.001). The overexpression of miR-106b was remarkable correlated with the lymphatic node metastasis (P = 0.038), clinical stage (P = 0.017) and differentiation (P = 0.009). ROC curve suggested that miR-106b was an effective diagnostic biomarker in CCA with the AUC of 0.913. The optimal cutoff value was 2.525, with the sensitivity of 89.7% and the specificity of 79.3%. Conclusions MiR-106b functions as an oncogene in CCA, which may be an potential diagnostic biomarker for CCA.

Sign in / Sign up

Export Citation Format

Share Document