34 research outputs found

    Lithium Suppresses Astrogliogenesis by Neural Stem and Progenitor Cells by Inhibiting STAT3 Pathway Independently of Glycogen Synthase Kinase 3 Beta

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    Transplanted neural stem and progenitor cells (NSCs) produce mostly astrocytes in injured spinal cords. Lithium stimulates neurogenesis by inhibiting GSK3b (glycogen synthetase kinase 3-beta) and increasing WNT/beta catenin. Lithium suppresses astrogliogenesis but the mechanisms were unclear. We cultured NSCs from subventricular zone of neonatal rats and showed that lithium reduced NSC production of astrocytes as well as proliferation of glia restricted progenitor (GRP) cells. Lithium strongly inhibited STAT3 (signal transducer and activator of transcription 3) activation, a messenger system known to promote astrogliogenesis and cancer. Lithium abolished STAT3 activation and astrogliogenesis induced by a STAT3 agonist AICAR (5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside), suggesting that lithium suppresses astrogliogenesis by inhibiting STAT3. GSK3Ξ² inhibition either by a specific GSK3Ξ² inhibitor SB216763 or overexpression of GID5-6 (GSK3Ξ² Interaction Domain aa380 to 404) did not suppress astrogliogenesis and GRP proliferation. GSK3Ξ² inhibition also did not suppress STAT3 activation. Together, these results indicate that lithium inhibits astrogliogenesis through non-GSK3Ξ²-mediated inhibition of STAT. Lithium may increase efficacy of NSC transplants by increasing neurogenesis and reducing astrogliogenesis. Our results also may explain the strong safety record of lithium treatment of manic depression. Millions of people take high-dose (>1 gram/day) lithium carbonate for a lifetime. GSK3b inhibition increases WNT/beta catenin, associated with colon and other cancers. STAT3 inhibition may reduce risk for cancer

    The potential of high-rate GPS for strong ground motion assessment

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    We show that high-rate GPS can have a vital role to play in near real-time monitoring of potentially destructive earthquakes. We do this by investigating the potential of GPS in recording strong ground motions from earthquakes in Switzerland and Japan. The study uses finite-fault stochastic ground motion simulation based on Fourier amplitude spectra and duration models previously developed for both countries, allowing comparisons in terms of both Fourier and time domain characteristics (here the Peak Ground Velocity, PGV). We find that earthquakes of magnitude Mw>5.8 can be expected to be recorded by GPS in real-time at 10Β km distance, i.e. their Fourier spectrum exceeds the noise of the instruments enough to be used in strong motion seismology. Post-processing of GPS time series lowers the noise and can improve the minimum observable magnitude by 0.1-0.2. As GPS receivers can record at higher rates (> 10Β sps), we investigate which sampling rate is sufficient to optimally record earthquake signals and conclude that a minimum sampling rate of 5Β sps is recommended. This is driven by recording events at short distances (below 10Β km for magnitude 6 events and below 30Β km for magnitude 7 events). Furthermore, the Maximum Ground Velocity derived from GPS is compared to the actual PGV for synthetic signals from the stochastic simulations and the 2008 Mw=6.9 Iwate earthquake. The proposed model, confirmed by synthetic and empirical data, shows that a reliable estimate of PGV for events of about magnitude 7 and greater can be basically retrieved by GPS in real-time and could be included for instance in ShakeMaps for aiding post-event disaster management

    Single-frequency RTK GNSS positioning

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    Real Time Kinematic (RTK) GNSS positioning is a carrier-phase differential positioning technique depending upon the fixing of the carrier phase integer ambiguities to ensure cm- level positioning accuracy. It is up to now the most viable technique to achieve cm-level accuracy for kinematic positioning in post-processing mode and particularly in real time mode. (Odijk 2014) discussed RTK and Precise Point Positioning (PPP) techniques for single-frequency case. It is suggested that instantaneous ambiguity fixing is achievable for single-frequency multi-constellation RTK, but single-frequency PPP integer ambiguity fixing is more challenging due to the need of additional information like satellite hardware phase biases and ionospheric corrections. Thus, single-frequency RTK GNSS positioning is the most feasible technique to achieve centimeter-level high precision positioning in real time using low-cost single- frequency GNSS antennas and receivers. It is a promising technique, which answers the growing high-precision navigation demand from industrial drones, self-driving cars and automated farming in which low-cost is crucial to democratize its application. Compared to the expensive geodetic GNSS receivers and antennas, low-cost single-frequency GNSS antennas and receivers do have some limitations in their performances like larger measurement variance and less suppression off multipath errors. In this thesis, the variances of code and carrier phase measurements of the single-frequency antenna and u-blox receiver are analyzed through computing the empirical standard deviation of code and carrier phase residuals in zero baseline tests and short-baseline tests. Multiplying the obtained variances with a proper weighting function of the measurements, a realistic stochastic model is constructed. The author proposes a mixed weighting function, where both C/N0 and satellite elevation angle are taken into account to better dilute the multipath error’s effect. The antenna C/N0 pattern is modeled using measurements of geostationary satellites and this pattern is used as the input to the proposed mixed weighting function. The results show that the proposed weighting function can well detect and down-weight the multipath contaminated carrier phase measurements and leads to better RTK positioning accuracy. The author has also estimated the phase center variations of the Trimble Bullet III antenna by processing the GNSS measurements collected from 4 sessions with the antenna pointing to 0Β°, 90Β°, 180Β° and 270Β°. Applying the estimated antenna phase center variations to RTK processing indeed reduces the systematic trend and biases/offsets in the carrier-phase residuals. Finally, by comparing the GPS-only RTK solution with GPS + BeiDou and GPS + GLONASS solution, the results indicate that using more satellites from additional constellations can significantly increase the ratio of ambiguity-fixed to ambiguity-float solutions in single-frequency RTK GNSS positioning

    Preparation of Graphene Quantum Dots by Visible-Fenton Reaction and Ultrasensitive Label-Free Immunosensor for Detecting Lipovitellin of Paralichthys Olivaceus

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    The increasing levels of environmental estrogens are causing negative effects on water, soil, wildlife, and human beings; label-free immunosensors with high specificities and sensitivities are being developed to test estrogeneous chemicals in complex environmental conditions. For the first time, highly fluorescent graphene quantum dots (GQDs) were prepared using a visible-Fenton catalysis reaction with graphene oxide (GO) as a precursor. Different microscopy and spectroscopy techniques were employed to characterize the physical and chemical properties of the GQDs. Based on the fluorescence resonance energy transfer (FRET) between amino-functionalized GQDs conjugated with anti-lipovitellin monoclonal antibodies (Anti-Lv-mAb) and reduced graphene oxide (rGO), an ultrasensitive fluorescent “ON-OFF” label-free immunosensor for the detection of lipovitellin (Lv), a sensitive biomarker derived from Paralichthys olivaceus for environmental estrogen, has been established. The immunosensor has a wide linear test range (0.001–1500 ng/mL), a lower limit of detection (LOD, 0.9 pg/mL), excellent sensitivity (26,407.8 CPS/(ng/mL)), and high selectivity and reproducibility for Lv quantification. The results demonstrated that the visible-Fenton is a simple, mild, green, efficient, and general approach to fabricating GQDs, and the fluorescent “ON-OFF” immunosensor is an easy-to-use, time-saving, ultrasensitive, and accurate detection method for weak estrogenic activity

    Idiopathic pulmonary fibrosis will increase the risk of lung cancer

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    Objective: To review the studies investigating the increased risk of lung cancer in patients with idiopathic pulmonary fibrosis (IPF). Data sources Data cited in this review were obtained mainly from PubMed and Medline from 1999 to 2013 and highly regarded older publications were also included. Study selection We identified, retrieved and reviewed the information on the frequency, risk factors, anatomical features, histological types, clinical manifestations, computed tomography findings and underlying mechanisms of lung cancer in IPF patients. Results: The prevalence rates of lung cancer in patients with IPF (4.8% to 48%) are much higher than patients without IPF (2.0% to 6.4%). The risk factors for lung cancer in IPF include smoking, male gender, and age. Lung cancers often occur in the peripheral lung zones where fibrotic changes are predominant. Adenocarcinoma and squamous cell carcinoma are the most common types of lung cancer in patients with IPF. Radiologic features of these patients include peripherally located, ill-defined mass mimicking air-space disease. The underlying mechanisms of the development of lung cancer in patients with IPF have not been fully understood, but may include the inflammatory response, epithelial injury and/or abnormalities, aberrant fibroblast proliferation, epigenetic and genetic changes, reduced cell-to-cell communication, and activation of specific signaling pathways. Conclusions: These findings suggest that IPF is associated with increased lung cancer risk. It is necessary to raise the awareness of lung cancer risk in IPF patients among physicians and patients

    Ku80 is highly expressed in lung adenocarcinoma and promotes cisplatin resistance

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    Abstract Background Ku80 is crucially implicated in DNA repair, apoptosis, and chemoresistance. In this study, we aimed to assess the expression of Ku80 in clinical lung adenocarcinoma specimens, and investigate its role in the regulation of cisplatin sensitivity in cisplatin resistant human lung adenocarcinoma cells A549/DDP. Methods Tumor specimens and medical records of 106 patients with operable lung adenocarcinoma were obtained from 1998 to 2003. Ku80 mRNA and protein levels of the tumor samples, cultured human lung adenocarcinoma cells A549 cells and their cisplatin resistant variant A549/DDP cells were examined by reverse transcription PCR and western blot analysis. Ku80-specific siRNA or control scramble siRNA was transfected into A549/DDP cells, then cell sensitivity to cisplatin was examined by 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis was assessed by flow cytometric analysis. In addition, the levels of cleaved caspase-3 and cleaved PARP in the treated cells were detected by western blot analysis. Results Total 83.3% (20/24) cisplatin-resistant tumors had high Ku80 expression, while 8.3% (4/48) cisplatin-sensitive tumors had high Ku80 expression (p  Conclusions Ku80 expression level could predict the outcome and the sensitivity to cisplatin-based chemotherapy in patients with lung adenocarcima. Ku80-siRNA could be utilized as a therapeutic strategy to resensitize nonresponders to cisplatin.</p

    Relationship of chest CT score with clinical characteristics of 108 patients hospitalized with COVID-19 in Wuhan, China

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    BACKGROUND: In December 2019, the outbreak of a disease subsequently termed COVID-19 occurred in Wuhan, China. The number of cases increased rapidly and spread to six continents. However, there is limited information on the chest computed tomography (CT) results of affected patients. Chest CT can assess the severity of COVID-19 and has sufficient sensitivity to assess changes in response to glucocorticoid therapy. OBJECTIVE: Analyze COVID-19 patients to determine the relationships of clinical characteristics, chest CT score, and levels of inflammatory mediators. METHODS: This retrospective, single-center case series of 108 consecutive hospitalized patients with confirmed COVID-19 at Tongji Hospital, Tongji Medical College of HUST (Wuhan, China) examined patients admitted from January 28 to February 20, 2020. Patient demographics, comorbidities, clinical findings, chest CT results, and CT scores of affected lung parenchyma were recorded. The relationships between chest CT score with levels of systemic inflammatory mediators were determined. RESULTS: All patients exhibited signs of significant systemic inflammation, including increased levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, chest CT score, and a decreased lymphocyte (LY) count. Chest CT score had positive associations with white blood cell (WBC) count, CRP, ESR, procalcitonin, and abnormal coagulation function, and a negative association with LY count. Treatment with a glucocorticoid increased the LY count, reduced the CT score and CRP level, and improved coagulation function. CONCLUSIONS: COVID-19 infection is characterized by a systemic inflammatory response that affects the lungs, blood, digestive system, and circulatory systems. The chest CT score is a good indicator of the extent of systemic inflammation. Glucocorticoid treatment appears to reduce systemic inflammation in these patients

    Pulchinenosides from Pulsatilla Chinensis Increase P-Glycoprotein Activity and Induce P-Glycoprotein Expression

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    Five pulchinenosides (pulchinenoside B3, pulchinenoside BD, pulchinenoside B7, pulchinenoside B10, and pulchinenoside B11) isolated from Pulsatilla chinensis (Bge) Regel saponins extract exhibited strong antitumor activities but poor gastrointestinal absorption properties. The enteric induction of P-glycoprotein (P-gp) is understood to restrict the oral bioavailability of some pharmaceutical compounds and lead to adverse drug reactions. Therefore, the present investigation was intended to delineate the impacts of pulchinenosides on cellular P-gp function and expression using Sf9 membrane vesicles and LS180 cells as a surrogate of human intestinal epithelial cells. Preliminary cytotoxic studies showed that 10 μM was an acceptable concentration for cytotoxicity and antiproliferation studies for all pulchinenosides using the alamarBlue assay. The cell cycle of LS180 cells detected by flow cytometry was not significantly influenced after 48 hours of coincubation with 10 μM of pulchinenosides. In the presence of pulchinenosides, the ATP-dependent transport of N-methyl-quinidine mediated by P-glycoprotein was stimulated significantly. The upregulation of P-glycoprotein and mRNA levels was found by Western blot and real-time PCR analysis in LS180 cells. Parallel changes indicate that all pulchinenosides are exposed to pulchinenosides-mediated transcriptional regulation. In conclusion, pulchinenosides could induce P-glycoprotein expression and directly increase its functional activity
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