A holy grail of curing neurodegenerative diseases is to identify the main causes and mechanisms underlying neuronal death. Many studies have sought to identify these targets in a wide variety of ways, but a more important task is to identify critical molecular targets and their origins. Potential molecular targets include advanced glycation end products (AGEs) that can promote neuronal cell death, thereby contributing to neurodegenerative disorders such as Alzheimer disease or Parkinson disease. In this study, we showed that AGE-albumin (glycated albumin) is synthesized in microglial cells and secreted in the human brain. Our results provide new insight into which microglial cells can promote the receptor for AGE-mediated neuronal cell death, eventually leading to neurodegenerative diseases.

Transforming growth factor-β1 (TGF-β1) is an important anti-inflammatory cytokine that modulates and resolves inflammatory responses. Recent studies have demonstrated that inflammation enhances neoplastic risk and potentiates tumor progression. In the evolution of cancer, pro-inflammatory cytokines such as IL-1β must overcome the anti-inflammatory effects of TGF-β to boost pro-inflammatory responses in epithelial cells. Here we show that IL-1β or Lipopolysaccharide (LPS) suppresses TGF-β-induced anti-inflammatory signaling in a NF-κB-independent manner. TRAF6, a key molecule in IL-1β signaling, mediates this suppressive effect through interaction with the type III TGF-β receptor (TβRIII), which is TGF-β-dependent and requires type I TGF-β receptor (TβRI) kinase activity. TβRI phosphorylates TβRIII at residue S829, which promotes the TRAF6/TβRIII interaction and consequent sequestration of TβRIII from the TβRII/TβRI complex. Our data indicate that IL-1β enhances the pro-inflammatory response by suppressing TGF-βsignaling through TRAF6-mediated sequestration of TβRIII, which may be an important contributor to the early stages of tumor progression.

BACKGROUND/AIMS The incidence of Hepatitis B has significantly declined since the introduction of an HBV vaccination program. The aim of this study was to investigate recent clinical features of acute viral hepatitis B (AVH-B) in Korea. METHODS A total of 2241 patients with acute viral hepatitis were enrolled and their data were collected from nine medical-centers between January 2006 and December 2009. RESULTS One hundred nineteen (5.3%) of the 2241 were diagnosed as AVH-B. Among 78 patients with AVH-B whose data were analyzed, 50 were male, and the mean age was 38.6 years. In an initial test, mean AST, ALT and total-bilirubin levels were 1296.2 IU/L, 2109.6 IU/L and 9.3 mg/dl, respectively. Positivity frequencies for HBeAg and anti-HBe were 55.1% and 67.9%, respectively, and the mean HBV DNA level was 5.2 log10 copies/ml. The mean length of hospitalization was 11.6 days. During follow-up, AST, ALT and total bilirubin levels were normalized or near-normalized in all patients without serious complications. Sixty-three of 66 (95.4%) patients showed HBsAg loss and 37 (56.1%) patients showed HBsAg seroconversion. Only 3 patients (4.5%) showed persistent hepatitis B viremia. There was no case of death or liver transplantation. Nine patients (11.3%) had received anti-viral agents and their clinical outcomes were not significantly different from those of patients treated without antiviral agents. CONCLUSIONS The prevalence of AVH-B among acute hepatitis patients is relatively low in Korea. AVH-B infection can be cured without complications in almost all patients, regardless of antiviral treatment.

BACKGROUND/AIMS We investigated the durability of the biochemical and virologic responses after adefovir (ADV) discontinuation in lamivudine-resistant (LMV-R) chronic hepatitis B (CHB) patients, and the outcomes of ADV discontinuation compared to that of ADV maintenance. METHODS The indication for ADV treatment cessation was an undetectable level of hepatitis B virus (HBV) DNA documented on two occasions at least 6 months apart. All patients received additional ADV for at least 12 months after the confirmation of undetectable HBV DNA (Cobas TaqMan PCR assay,<70 copies/mL). Of 36 patients who had a sufficient ADV therapeutic effect, 19 discontinued ADV treatment, while the others maintained it. A virologic rebound was arbitrarily defined as the redetection of HBV DNA at a level higher than 10(5) copies/mL. RESULTS In the ADV discontinuation group, ADV treatment and additional therapy were administered for medians of 33 months (range, 12-47 months) and 18 months, respectively. The patients were followed for a median of 12 months (range, 3-30 months) after ADV cessation. During that period, 18 of 19 patients (95%) experienced viral relapse. Viral rebound was observed in six patients (32%). However, 12 of 18 patients (67%) exhibited serum HBV DNA levels of less than (5) copies/mL. Biochemical relapses were observed in four of the six patients with viral rebound. In the ADV maintenance group, patients were treated for a median of 53 months (range, 31-85 months), and 9 patients (53%) experienced viral breakthrough. CONCLUSIONS During short-term follow-up after ADV discontinuation, most patients (95%) exhibited viral relapse, whereas and viral breakthrough occurred in about half of patients (53%) maintained on ADV therapy. Therefore, the durability of virologic response after ADV discontinuation in LMV-R patients was unsatisfactory. In addition, and viral breakthrough was not infrequent in the ADV continuation group.

A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation.

Generation of induced pluripotent stem cells (iPSCs) has revolutionized the field of regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. iPSCs can self-renew and can differentiate into many cell types, offering a potentially unlimited source of cells for targeted differentiation into somatic effector cells. Hence, iPSCs are likely to be invaluable for therapeutic applications and disease-related research. In this review, we summarize the recent progress of iPSC generation that has been made with an emphasis on both basic and clinical applications including disease modeling, drug toxicity screening/drug discovery and cell replacement therapy.

BACKGROUND: Suppression of hepatitis B virus (HBV) DNA is more potent, and occurrence of resistant strain is rare with entecavir than lamivudine, but whether these merits result in a more favourable outcome in HBV-related decompensated cirrhosis patients is unclear. AIMS: To compare virologic response, changes in liver function, clinical course and predictive factors for early mortality after treatment between patients treated with lamivudine and those with entecavir in HBV-related decompensated cirrhosis patients. METHODS: HBV-related decompensated cirrhosis patients [Child-Turcotte-Pugh (CTP) score ≥ 7] treated with either lamivudine or entecavir were enrolled. Serum HBV DNA levels, CTP score and Model for End-stage Liver Disease (MELD) score were monitored every 3 months. RESULTS: Eighty-six patients were enrolled; mean age was 54 ± 11 years, and 63 (73.3%) patients were men; 41 (47.7%) and 45 (52.3%) patients were assigned to the lamivudine group and entecavir group respectively. Although suppression of serum HBV DNA level was more potent in the entecavir group, CTP or MELD scores during the course of treatment did not differ between the two groups. Similarly, 6-month survival rates did not differ between the two groups (95.1 vs 93.2%, P = 0.684). Baseline CTP score and MELD score at 3 months of treatment were significantly associated with 6-month mortality. The 6- and 12-month mortality rates for patients with baseline CTP score ≥11 and MELD score ≥17.5 after 3 months of treatment were 42.9 and 61.9% respectively. CONCLUSIONS: Although HBV DNA suppression was more potent in the entecavir group than the lamivudine group, early mortality rates did not differ between the two groups. The baseline CTP score and MELD score 3 months after initiating antiviral treatment were significant predictors of early mortality.

We report a graphene-polymer hybrid nanostructure-based bioenergy storage device to turn on and off biomotor activity in real-time. In this strategy, graphene was functionalized with amine groups and utilized as a transparent electrode supporting the motility of biomotors. Conducting polymer patterns doped with adenosine triphosphate (ATP) were fabricated on the graphene and utilized for the fast release of ATP by electrical stimuli through the graphene. The controlled release of biomotor fuel, ATP, allowed us to control the actin filament transportation propelled by the biomotor in real-time. This strategy should enable the integrated nanodevices for the real-time control of biological motors, which can be a significant stepping stone toward hybrid nanomechanical systems based on motor proteins.

We developed a scanning noise microscopy (SNM) method and demonstrated the nanoscale noise analysis of a graphene strip-based device. Here, a Pt tip made a direct contact on the surface of a nanodevice to measure the current noise spectrum through it. Then, the measured noise spectrum was analyzed by an empirical model to extract the noise characteristics only from the device channel. As a proof of concept, we demonstrated the scaling behavior analysis of the noise in graphene strips. Furthermore, we performed the nanoscale noise mapping on a graphene channel, allowing us to study the effect of structural defects on the noise of the graphene channel. The SNM method is a powerful tool for nanoscale noise analysis and should play a significant role in basic research on nanoscale devices.