Lovastatin Corrects Excess Protein Synthesis and Prevents Epileptogenesis in a Mouse Model of Fragile X Syndrome

Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is widely prescribed for the treatment of high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent one of the robust functional consequences of increased protein synthesis in FXS, epileptogenesis. These data suggest that lovastatin is potentially disease modifying and could be a viable prophylactic treatment for epileptogenesis in FXS.FRAXA Research FoundationNational Institute of Mental Health (U.S.)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.)Simons Foundatio

Application of Flexible Micro Temperature Sensor in Oxidative Steam Reforming by a Methanol Micro Reformer

Advances in fuel cell applications reflect the ability of reformers to produce hydrogen. This work presents a flexible micro temperature sensor that is fabricated based on micro-electro-mechanical systems (MEMS) technology and integrated into a flat micro methanol reformer to observe the conditions inside that reformer. The micro temperature sensor has higher accuracy and sensitivity than a conventionally adopted thermocouple. Despite various micro temperature sensor applications, integrated micro reformers are still relatively new. This work proposes a novel method for integrating micro methanol reformers and micro temperature sensors, subsequently increasing the methanol conversion rate and the hydrogen production rate by varying the fuel supply rate and the water/methanol ratio. Importantly, the proposed micro temperature sensor adequately controls the interior temperature during oxidative steam reforming of methanol (OSRM), with the relevant parameters optimized as well

Ultra high-resolution fMRI and electrophysiology of the rat primary somatosensory cortex

High-resolution functional-magnetic-resonance-imaging (fMRI) has been used to study brain functions at increasingly finer scale, but whether fMRI can accurately reflect layer-specific neuronal activities is less well understood. The present study investigated layer-specific cerebral-blood-volume (CBV) fMRI and electrophysiological responses in the rat cortex. CBV fMRI at 40×40 µm in-plane resolution was performed on an 11.7-T scanner. Electrophysiology used a 32-channel electrode array that spanned the entire cortical depth. Graded electrical stimulation was used to study activations in different cortical layers, exploiting the notion that most of the sensory-specific neurons are in layers II–V and most of the nociceptive-specific neurons are in layers V–VI. CBV response was strongest in layer IV of all stimulus amplitudes. Current source density analysis showed strong sink currents at cortical layers IV and VI. Multi-unit activities mainly appeared at layers IV–VI and peaked at layer V. Although our measures showed scaled activation profiles during modulation of stimulus amplitude and failed to detect specific recruitment at layers V and VI during noxious electrical stimuli, there appears to be discordance between CBV fMRI and electrophysiological peak responses, suggesting neurovascular uncoupling at laminar resolution. The technique implemented in the present study offers a means to investigate intracortical neurovascular function in the normal and diseased animal models at laminar resolution

2-O-Methylmagnolol Induces Apoptosis and Inhibits IL-6/STAT3 Signaling in Oral Squamous Cell Carcinoma

Background/Aims: 2-O-methylmagnolol (MM1), a derivative of magnolol bearing one methoxy moiety, has been shown to display improved anti-tumor activity against skin cancers. In this study, we examined the anti-tumor effects of magnolol and MM1 on oral squamous cell carcinoma (OSCC). Methods: Trypane blue staining and clonogenic assays were performed to determine the cytotoxic effects of magnolol and MM1 in OSCC cells. Migration and matrigel invasion assays were carried out to examine the metastasis effects of magnolol and MM1 in OSCC cells. IL6-stimulation, Western blot, and immunohistochemistry were used to investigate the IL-6/STAT3 signaling and apoptosis. A bioluminescent mouse model of orthotopically implanted SAS cells was used to determine the anti-tumor activity of MM1 in vivo. Results: MM1 displays greater activity than magnolol on affecting the cytotoxicity, migration, and invasion of OSCC cells cultured in vitro. The improved anti-tumor activity of MM1 was shown to associate with its greater activity to inhibit STAT3 signaling and to induce apoptosis in the OSCC. In addition, we presented evidence that MM1 is effective in inhibiting the growth of orthotopic implanted OSCC cells in vivo. Conclusion: Our data indicate that MM1 displays greater anti-tumor activity than magnolol in OSCC and is an attractive agent to be further explored for its potential clinical application

Cell volume restriction by mercury chloride reduces M1-like inflammatory response of bone marrow-derived macrophages

Dysregulation of macrophages in the pro-inflammatory (M1) and anti-inflammatory (M2) sub-phenotypes is a crucial element in several inflammation-related diseases and injuries. We investigated the role of aquaporin (AQP) in macrophage polarization using AQP pan-inhibitor mercury chloride (HgCl2). Lipopolysaccharides (LPSs) induced the expression of AQP-1 and AQP-9 which increased the cell size of bone marrow-derived macrophages. The inhibition of AQPs by HgCl2 abolished cell size changes and significantly suppressed M1 polarization. HgCl2 significantly reduced the activation of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways and inhibited the production of IL-1β. HgCl2 attenuated LPS-induced activation of mitochondria and reactive oxygen species production and autophagy was promoted by HgCl2. The increase in the light chain three II/light chain three I ratio and the reduction in PTEN-induced kinase one expression suggests the recycling of damaged mitochondria and the restoration of mitochondrial activity by HgCl2. In summary, the present study demonstrates a possible mechanism of the AQP inhibitor HgCl2 in macrophage M1 polarization through the restriction of cell volume change, suppression of the p38 MAPK/NFκB pathway, and promotion of autophagy

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored

Anemia risk in relation to lead exposure in lead-related manufacturing

Abstract Background Lead-exposed workers may suffer adverse health effects under the currently regulated blood lead (BPb) levels. However, a probabilistic assessment about lead exposure-associated anemia risk is lacking. The goal of this study was to examine the association between lead exposure and anemia risk among factory workers in Taiwan. Methods We first collated BPb and indicators of hematopoietic function data via health examination records that included 533 male and 218 female lead-exposed workers between 2012 and 2014. We used benchmark dose (BMD) modeling to estimate the critical effect doses for detection of abnormal indicators. A risk-based probabilistic model was used to characterize the potential hazard of lead poisoning for job-specific workers by hazard index (HI). We applied Bayesian decision analysis to determine whether BMD could be implicated as a suitable BPb standard. Results Our results indicated that HI for total lead-exposed workers was 0.78 (95% confidence interval: 0.50–1.26) with risk occurrence probability of 11.1%. The abnormal risk of anemia indicators for male and female workers could be reduced, respectively, by 67–77% and 86–95% by adopting the suggested BPb standards of 25 and 15 μg/dL. Conclusions We conclude that cumulative exposure to lead in the workplace was significantly associated with anemia risk. This study suggests that current BPb standard needs to be better understood for the application of lead-exposed population protection in different scenarios to provide a novel standard for health management. Low-level lead exposure risk is an occupational and public health problem that should be paid more attention