scholarly journals High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ahmed M. Abu El-Asrar ◽  
Mohd Imtiaz Nawaz ◽  
Mohammad Mairaj Siddiquei ◽  
Abdullah S. Al-Kharashi ◽  
Dustan Kangave ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
High Mobility ◽  
Brain Derived Neurotrophic Factor ◽  
High Mobility Group ◽  
Intercellular Adhesion Molecule ◽  
Diabetic Patients ◽  
Intercellular Adhesion Molecule 1 ◽  
Serum Samples ◽  
Monocyte Chemoattractant Protein 1 ◽  
Diabetic Retina

To test the hypothesis that brain-derived neurotrophic factor-(BDNF-) mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration.

scholarly journals Early Release of HMGB-1 from Neurons after the Onset of Brain Ischemia

2007 ◽  
Vol 28 (5) ◽  
pp. 927-938 ◽  
Author(s):  
Jianhua Qiu ◽  
Masaki Nishimura ◽  
Yumei Wang ◽  
John R Sims ◽  
Sumei Qiu ◽  
...  
Keyword(s):  
Brain Ischemia ◽  
High Mobility ◽  
High Mobility Group ◽  
Glutamate Excitotoxicity ◽  
Intercellular Adhesion Molecule ◽  
Normal Brain ◽  
Intercellular Adhesion Molecule 1 ◽  
Neuronal Marker ◽  
Ischemic Reperfusion

The nuclear protein high-mobility group box 1 (HMGB-1) promotes inflammation in sepsis, but little is known about its role in brain ischemia-induced inflammation. We report that HMGB-1 and its receptors, receptor for advanced glycation end products (RAGE), Toll-like receptor 2 (TLR2), and TLR4, were expressed in normal brain and in cultured neurons, endothelia, and glial cells. During middle cerebral artery occlusion (MCAO), in mice, HMGB-1 immunostaining rapidly disappeared from all cells within the striatal ischemic core from 1 h after onset of occlusion. High-mobility group box 1 translocation from nucleus to cytoplasm was observed within the cortical periinfarct regions 2 h after ischemic reperfusion (2 h MCAO). High-mobility group box 1 predominantly translocated to the cytoplasm or disappeared in cells that colabeled with the neuronal marker NeuN. Furthermore, RAGE was robustly expressed in the periinfarct region after MCAO. Cellular release of HMGB-1 was detected by immunoblotting of cerebrospinal fluid as early as 2 h after ischemic reperfusion (2 h MCAO). High-mobility group box 1 released from neurons, in vitro, after glutamate excitotoxicity, maintained biologic activity and induced glial expression of tumor necrosis factor α (TNFα). Anti-HMGB-1 antibody suppressed TNFα upregulation in astrocytes exposed to conditioned media from glutamate-treated neurons. Moreover, TNFα and the cytokine intercellular adhesion molecule-1 increased in cultured glia and endothelial cells, respectively, after adding recombinant HMGB-1. In conclusion, HMGB-1 is released early after ischemic injury from neurons and may contribute to the initial stages of the inflammatory response.

scholarly journals 0044 Association Between Chronotype and Circulating Levels of Interleukin-6 in Colorectal Cancer Patients: Preliminary Results from the ColoCare Study

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A18-A18
Author(s):  
A R Peoples ◽  
B Gigic ◽  
J Ose ◽  
C Himbert ◽  
S Hardikar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Serum Samples ◽  
Meso Scale Discovery ◽  
Monocyte Chemoattractant Protein 1 ◽  
Colorectal Cancer Patients ◽  
Morning Type

Abstract Introduction Accumulating evidence suggests that chronotype, i.e., circadian topology of an individual indicating morning or evening type, is associated with inflammation. To date, no study has examined the relationship between chronotype and inflammation in colorectal cancer patients. We investigated the associations between chronotype and inflammatory and angiogenesis biomarkers in colorectal cancer patients. Methods We used pre-surgery serum samples from n=67 newly diagnosed colorectal cancer patients (stage I-IV) recruited at the ColoCare Study site in Heidelberg, Germany. The ColoCare Study is an ongoing, international, multisite, prospective cohort study in colorectal cancer patients. Inflammatory and angiogenesis biomarkers [c-reactive protein (CRP), interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1)] were measured at the Huntsman Cancer Institute, USA using the Meso Scale Discovery platform and were log transformed. Chronotype was assessed prior to surgery with the reduced Morningness-Eveningness Questionnaire (rMEQ; scale 4–25; a higher score indicates more morning-type). Patients were dichotomized, based on the median values for rMEQ, into 2 groups: rMEQ-low (score≤16.0; n=35; indicating more evening-type) or rMEQ-high (score>16.0; n=32; indicating more morning-type). Results Using Mann-Whitney U test, we observed that rMEQ-low group (i.e., more evening-type) compared to rMEQ-high group (i.e., more morning-type) had approx. two times significantly higher levels of log transformed IL-6 (mean=2.24 vs. 1.30; U=382.0; Z=-2.23; p=0.03), but not for other inflammatory or angiogenesis biomarkers. This association between chronotype and IL-6 was maintained even after adjusting for age, sex, tumor stage, tumor site, and sleep duration using a generalized estimating equations model (adjusted mean difference=1.10; 95% confidence interval=0.33, 1.88; p=0.01; effect size, Cohen’s d=0.69). Conclusion These preliminary findings suggest that the evening chronotype is associated with increased IL-6 inflammatory biomarker in colorectal cancer patients. Further research is needed to confirm and understand the mechanistic underpinnings of the observed results. Support Funding: NCI U01 CA206110, R01 CA189184, and R01 CA207371.

scholarly journals Osteopontin Predicts Three-Month Outcome in Stroke Patients Treated by Reperfusion Therapies

2020 ◽  
Vol 9 (12) ◽  
pp. 4028
Author(s):  
Elena Meseguer ◽  
Devy Diallo ◽  
Julien Labreuche ◽  
Hugo Charles ◽  
Sandrine Delbosc ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Tissue Remodeling ◽  
Intercellular Adhesion Molecule ◽  
Cathepsin S ◽  
Intercellular Adhesion Molecule 1 ◽  
Stroke Patients ◽  
Monocyte Chemoattractant Protein 1 ◽  
Significance Level ◽  
Matrix Metallopeptidase

Establishing a prognosis at hospital admission after stroke is a major challenge. Inflammatory processes, hemostasis, vascular injury, and tissue remodeling are all involved in the early response to stroke. This study analyzes whether 22 selected biomarkers, sampled at admission, predict clinical outcomes in 153 stroke patients treated by thrombolysis and mechanical endovascular treatment (MET). Biomarkers were related to hemostasis (u-plasminogen activator/urokinase (uPA/urokinase), serpin E1/PAI-1, serpin C1/antithrombin-III, kallikrein 6/neurosin, alpha 2-macroglobulin), inflammation[myloperoxidase (MPO), chemokine ligand 2/monocyte chemoattractant protein-1 chemokine (CCL2/MCP-1), adiponectin, resistin, cell-free DNA (cDNA), CD40 Ligand (CD40L)], endothelium activation (Vascular cell adhesion protein 1 (VCAM-1) intercellular adhesion molecule 1 (ICAM-1), platelet endothelial cell adhesion molecule 1 (CD31/PECAM-1)], and tissue remodeling (total cathepsin S, osteopontin, cystatin C, neuropilin-1, matrix metallopeptidase 2 (MMP-2), matrix metallopeptidase 3 (MMP-3), matrix metallopeptidase 9 (MMP-9), matrix metallopeptidase 13 (MMP-13)]. Correlations between their levels and excellent neurological improvement (ENI) at 24 h and good outcomes (mRS 0–2) at three months were tested. Osteopontin and favorable outcomes reached the significance level (p = 0.008); the adjusted OR per SD increase in log-transformed osteopontin was 0.34 (95%CI, 0.18–0.62). The relationship between total cathepsin S and MPO with ENI, was borderline of significance (p = 0.064); the adjusted OR per SD increase in log-transformed of total cathepsin S and MPO was 0.54 (95%CI, 0.35–0.81) and 0.51 (95%CI, 0.32–0.80), respectively. In conclusion, osteopontin levels predicted three-month favorable outcomes, supporting the use of this biomarker as a complement of clinical and radiological parameters for predicting stroke prognosis.

High-mobility group box-1 protein activates inflammatory signaling pathway components and disrupts retinal vascular-barrier in the diabetic retina

2013 ◽  
Vol 107 ◽  
pp. 101-109 ◽  
Author(s):  
Ghulam Mohammad ◽  
Mohammad Mairaj Siddiquei ◽  
Amira Othman ◽  
Mohamed Al-Shabrawey ◽  
Ahmed M. Abu El-Asrar
Keyword(s):  
Signaling Pathway ◽  
High Mobility ◽  
High Mobility Group ◽  
Inflammatory Signaling ◽  
Diabetic Retina
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