Inhibitory effect of a tyrosine-fructose Maillard reaction product, 2,4-bis(p-hydroxyphenyl)-2-butenal on amyloid-β generation and inflammatory reactions via inhibition of NF-κB and STAT3 activation in cultured astrocytes and microglial BV-2 cells

<p>Abstract</p> <p>Background</p> <p>Amyloidogenesis is linked to neuroinflammation. The tyrosine-fructose Maillard reaction product, 2,4-bis(<it>p</it>-hydroxyphenyl)-2-butenal, possesses anti-inflammatory properties in cultured macrophages, and in an arthritis animal model. Because astrocytes and microglia are responsible for amyloidogenesis and inflammatory reactions in the brain, we investigated the anti-inflammatory and anti-amyloidogenic effects of 2,4-bis(<it>p</it>-hydroxyphenyl)-2-butenal in lipopolysaccharide (LPS)-stimulated astrocytes and microglial BV-2 cells.</p> <p>Methods</p> <p>Cultured astrocytes and microglial BV-2 cells were treated with LPS (1 μg/ml) for 24 h, in the presence (1, 2, 5 μM) or absence of 2,4-bis(<it>p</it>-hydroxyphenyl)-2-butenal, and harvested. We performed molecular biological analyses to determine the levels of inflammatory and amyloid-related proteins and molecules, cytokines, Aβ, and secretases activity. Nuclear factor-kappa B (NF-κB) DNA binding activity was determined using gel mobility shift assays.</p> <p>Results</p> <p>We found that 2,4-bis(<it>p</it>-hydroxyphenyl)-2-butenal (1, 2, 5 μM) suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in LPS (1 μg/ml)-stimulated astrocytes and microglial BV-2 cells. Further, 2,4-bis(<it>p</it>-hydroxyphenyl)-2-butenal inhibited the transcriptional and DNA binding activity of NF-κB--a transcription factor that regulates genes involved in neuroinflammation and amyloidogenesis via inhibition of IκB degradation as well as nuclear translocation of p50 and p65. Consistent with the inhibitory effect on inflammatory reactions, 2,4-bis(<it>p</it>-hydroxyphenyl)-2-butenal inhibited LPS-elevated Aβ₄₂levels through attenuation of β- and γ-secretase activities. Moreover, studies using signal transducer and activator of transcription 3 (STAT3) siRNA and a pharmacological inhibitor showed that 2,4-bis(<it>p</it>-hydroxyphenyl)-2-butenal inhibits LPS-induced activation of STAT3.</p> <p>Conclusions</p> <p>These results indicate that 2,4-bis(<it>p</it>-hydroxyphenyl)-2-butenal inhibits neuroinflammatory reactions and amyloidogenesis through inhibition of NF-κB and STAT3 activation, and suggest that 2,4-bis(<it>p</it>-hydroxyphenyl)-2-butenal may be useful for the treatment of neuroinflammatory diseases like Alzheimer's disease.</p

Ubi-RKE: A Rhythm Key Based Encryption Scheme for Ubiquitous Devices

As intelligent ubiquitous devices become more popular, security threats targeting them are increasing; security is seen as one of the major challenges of the ubiquitous computing. Now a days, applying ubiquitous computing in number of fields for human safety and convenience was immensely increased in recent years. The popularity of the technology is rising day by day, and hence the security is becoming the main focused point with the advent and rising popularity of the applications. In particular, the number of wireless networks based on ubiquitous devices has increased rapidly; these devices support transmission for many types of data traffic. The convenient portability of ubiquitous devices makes them vulnerable to security threats, such as loss, theft, data modification, and wiretapping. Developers and users should seriously consider employing data encryption to protect data from such vulnerabilities. In this paper, we propose a Rhythm Key based Encryption scheme for ubiquitous devices (Ubi-RKE). The concept of Rhythm Key based Encryption has been applied to numerous real world applications in different domains. It provides key memorability and secure encryption through user touching rhythm on ubiquitous devices. Our proposed scheme is more efficient for users than existing schemes, by providing a strong cipher

Genetic variants of interferon lambda-related genes and chronic kidney disease susceptibility in the Korean population

Background Chronic kidney disease (CKD) is a common condition leading to renal dysfunction and is closely related to increased cardiovascular and mortality risk. CKD is an important public health issue, and recent genetic studies have verified common CKD susceptibility variants. This research examines the interrelationship between candidate genes polymorphisms of interferon lambda (IFNL) induction, its signaling pathway, and CKD. Methods Seventy-five patients with advanced CKD and 312 healthy subjects (as controls) participated in this research. A replication set composed of 172 patients with advanced CKD and 365 controls was used for additional analysis. The genotype of single nucleotide polymorphisms (SNPs) was determined by the Axiom Genome-Wide Human Assay and SNaPshot assay. Results The SNP of IFNL3 was significantly associated with CKD in the codominant (p = 0.02) and dominant models (p = 0.02). In addition, the SNPs of IFNL2 were significantly associated with CKD in the dominant model (p = 0.03), and the SNP of interferon alpha receptor 2 (IFNAR2) was significantly associated with CKD in the log-additive model (p = 0.03). Concerning rs148543092, in the IFNL3 gene, a significant association was observed after pooling the original and replication sets. Conclusion These results indicate that SNPs in the IFNL induction and signal pathway may be associated with CKD risk in the Korean population. Finally, our results also show that the IFNL3 gene variant may be associated with CKD risk

Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production

A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6) to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 µM ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release). Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK), and different mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2) as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A2 formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia

Subclinical Cervical Osteochondroma Presenting as Brown-Sequard Syndrome after Trivial Neck Trauma

Osteochondroma is a rare condition in the spine that may be indolent due to its slow growth. The authors present a case of 32-year-old man with subclinical osteochondroma in the cervical spine presenting as Brown-Sequard syndrome after trivial neck trauma. After resection of the tumor through hemilaminectomy, his symptoms were improved with mild residual sequelae

Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage

Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases