MMP-3 Contributes to Nigrostriatal Dopaminergic Neuronal Loss, BBB Damage, and Neuroinflammation in an MPTP Mouse Model of Parkinson\u27s Disease

The present study examined whether matrix metalloproteinase-3 (MMP-3) participates in the loss of dopaminergic (DA) neurons in the nigrostriatal pathway in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson\u27s disease with blood brain barrier (BBB) damage and infiltration of peripheral immune cells. Tyrosine hydroxylase (TH) immunostaining of brain sections from MPTP-treated mice showed that MPTP induced significant degeneration of nigrostriatal DA neurons. Moreover, FITC-labeled albumin detection and immunostaining revealed that MPTP caused damage to the BBB and increased the number of ED-1- and CD-3-immunopositive cells in the substantia nigra (SN). Genetic ablation of MMP-3 reduced the nigrostriatal DA neuron loss and improved motor function. This neuroprotective effect afforded by MMP-3 deletion was associated with the suppression of BBB disruption and a decrease in the number of ED-1- and CD-3-immunopositive cells in the SN. These data suggest that MMP-3 could play a crucial role in neurodegenerative diseases such as PD in which BBB damage and neuroinflammation are implicated

Expression of CYLD and NF-κB in Human Cholesteatoma Epithelium

The tumor suppressor CYLD is a deubiquitinating enzyme that inhibits activation of the NF-κB, which has key roles in inflammation and apoptosis. We hypothesized that CYLD may regulate the NF-κB signaling pathway in cholesteatoma. We conducted immunohistochemistry to examine the expression of CYLD and NF-κB in 16 cases of cholesteatoma and paired cases of retroauricular (RA) skin. In cholesteatoma epithelium, activated NF-κ B expression was significantly higher than in RA skin, whereas CYLD expression was significantly lower in cholesteatoma epithelium than in RA skin (P < .05). Furthermore, a significant inverse correlation was detected between CYLD and activated NF-κB expression in cholesteatoma epithelium (r = −0.630). We found that CYLD reduced and activated increased NF-κB in cholesteatoma epithelium in comparison to RA skin. The inverse correlation between CYLD and activated NF-κB in cholesteatoma may be involved in cholesteatoma epithelial hyperplasia

MMP-3 Contributes to Nigrostriatal Dopaminergic Neuronal Loss, BBB Damage, and Neuroinflammation in an MPTP Mouse Model of Parkinson’s Disease

The present study examined whether matrix metalloproteinase-3 (MMP-3) participates in the loss of dopaminergic (DA) neurons in the nigrostriatal pathway in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease with blood brain barrier (BBB) damage and infiltration of peripheral immune cells. Tyrosine hydroxylase (TH) immunostaining of brain sections from MPTP-treated mice showed that MPTP induced significant degeneration of nigrostriatal DA neurons. Moreover, FITC-labeled albumin detection and immunostaining revealed that MPTP caused damage to the BBB and increased the number of ED-1- and CD-3-immunopositive cells in the substantia nigra (SN). Genetic ablation of MMP-3 reduced the nigrostriatal DA neuron loss and improved motor function. This neuroprotective effect afforded by MMP-3 deletion was associated with the suppression of BBB disruption and a decrease in the number of ED-1- and CD-3-immunopositive cells in the SN. These data suggest that MMP-3 could play a crucial role in neurodegenerative diseases such as PD in which BBB damage and neuroinflammation are implicated

Effect of multiple debris flow countermeasures on flow characteristics and topographic changes through real-scale experiment

In this study, to investigate the effect of multiple countermeasure on the flow characteristics of debris flows, a real-scale experiment was conducted in a natural gully by reproducing a debris flow with a installation of multiple countermeasures. In addition, the topographic changes before and after experiment by debris flow were investigated using UAV-LiDAR. Based on the experiment results, the effect of multiple countermeasures and the topographic changes against the gully erosion and deposition caused by debris flow were also analyzed. The installation of multiple countermeasures significantly decreased the frontal velocity of debris flow. Furthermore, the countermeasure induced the deposition of debris material on the back of the countermeasure

Effectiveness and safety of adalimumab in patients with intestinal Behçets disease: a real-world prospective observational study in South Korea

Background Intestinal Behçets disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. Methods This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçets disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). Results A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953–0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). Conclusion Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs

Ghrelin Inhibits Oligodendrocyte Cell Death by Attenuating Microglial Activation

BackgroundRecently, we reported the antiapoptotic effect of ghrelin in spinal cord injury-induced apoptotic cell death of oligodendrocytes. However, how ghrelin inhibits oligodendrocytes apoptosis, is still unknown. Therefore, in the present study, we examined whether ghrelin inhibits microglia activation and thereby inhibits oligodendrocyte apoptosis.MethodsUsing total cell extracts prepared from BV-2 cells activated by lipopolysaccharide (LPS) with or without ghrelin, the levels of p-p38 phosphor-p38 mitogen-activated protein kinase (p-p38MAPK), phospho-c-Jun N-terminal kinase (pJNK), p-c-Jun, and pro-nerve growth factor (proNGF) were examined by Western blot analysis. Reactive oxygen species (ROS) production was investigated by using dichlorodihydrofluorescein diacetate. To examine the effect of ghrelin on oligodendrocyte cell death, oligodendrocytes were cocultured in transwell chambers of 24-well plates with LPS-stimulated BV-2 cells. After 48 hours incubation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling staining were assessed.ResultsGhrelin treatment significantly decreased levels of p-p38MAPK, p-JNK, p-c-Jun, and proNGF in LPS-stimulated BV-2 cells. ROS production increased in LPS-stimulated BV-2 cells was also significantly inhibited by ghrelin treatment. In addition, ghrelin significantly inhibited oligodendrocyte cell death when cocultured with LPS-stimulated BV-2 cells.ConclusionGhrelin inhibits oligodendrocyte cell death by decreasing proNGF and ROS production as well as p38MAPK and JNK activation in activated microglia as an anti-inflammatory hormone

Effect of multiple debris flow countermeasures on flow characteristics and topographic changes through real-scale experiment

In this study, to investigate the effect of multiple countermeasure on the flow characteristics of debris flows, a real-scale experiment was conducted in a natural gully by reproducing a debris flow with a installation of multiple countermeasures. In addition, the topographic changes before and after experiment by debris flow were investigated using UAV-LiDAR. Based on the experiment results, the effect of multiple countermeasures and the topographic changes against the gully erosion and deposition caused by debris flow were also analyzed. The installation of multiple countermeasures significantly decreased the frontal velocity of debris flow. Furthermore, the countermeasure induced the deposition of debris material on the back of the countermeasure