2,754 research outputs found
Inhibitory effect of tetramethylpyrazine combined with propranolol on murine hemangioma endothelial cells
Purpose: To study the inhibitory effect of different doses of tetramethylpyrazine (TMP) combined with the beta-blocker, propranolol (Pro) on hemangioma endothelial (EOMA) cells.
Methods: EOMA cells were cultured in vitro with varying doses of TMP and Pro (5, 10, 20 and 40 uM). The effect of treatments on cell proliferation was assessed by MTT assay, while cell apoptosis was assayed by flow cytometry. The expressions of Bcl-2, Bax, p-mTOR), total-mammalian target of rapamycin (t-mTOR, p-p70S6) and total-p70 ribosomal protein S6 (t-p70S6) proteins were determined using Western blot.
Results: MTT data showed that when used alone, TMP had no significant inhibitory effect on EOMA cells (p > 0.05). However, when TMP was combined with propranolol, there was significant inhibition of EOMA cells, and that the inhibition is dependent on TMP dose. Flow cytometry results showed that the combination of TMP and Pro induced EOMA cell apoptosis dose-dependently (p < 0.05). Moreover, TMP dose-dependently inhibited the phosphorylation of mTOR and p70S6 in EOMA cells, and enhanced Bax expression, but downregulated Bcl-2 (p < 0.05).
Conclusion: These results suggest that TMP enhances the inhibitory influence of Pro p-mTOR and pp-70S6 in EOMA cells in a dose-dependent manner. Thus, TMP may enhance Pro-induced inhibition of the growth of endothelial cells, and promote apoptosis through suppression of activation of PI3K/AKT signal route. These findings provide a theoretical basis for the clinical application of TMP/Pro combination for the treatment of hemangioma
Ethanol Extract of the Flower Chrysanthemum morifolium Augments Pentobarbital-Induced Sleep Behaviors: Involvement of Cl− Channel Activation
Dried Chrysanthemum morifolium flowers have traditionally been used in Korea for the treatment
of insomnia. This study was performed to investigate whether the ethanol extract of Chrysanthemum
morifolium flowers (EFC) enhances pentobarbital-induced sleep behaviors. EFC prolonged sleep time
induced by pentobarbital similar to muscimol, a GABAA receptors agonist. EFC also increased sleep
rate and sleep time when administrated with pentobarbital at a subhypnotic dosage. Both EFC and
pentobarbital increased chloride (Cl−) influx in primary cultured cerebellar granule cells. EFC
increased glutamic acid decarboxylase (GAD) expression levels, but had no effect on the expression
of α1-, β2-, and γ2-subunits of the GABAA receptor in the hippocampus of a mouse brain. This is in
contrast to treatment with pentobarbital, which showed decreased α1-subunit expression and no
change in GAD expression. In conclusion, EFC augments pentobarbital-induced sleep behaviors;
these effects may result from Cl− channel activation
Probing Dirac Neutrino Properties with Dilepton Signature
The neutrinophilic two Higgs doublet model is one of the simplest models to
explain the origin of tiny Dirac neutrino masses. This model introduces a new
Higgs doublet with eV scale VEV to naturally generate the tiny neutrino masses.
Depending on the same Yukawa coupling, the neutrino oscillation patterns can be
probed with the dilepton signature from the decay of charged scalar .
For example, the normal hierarchy predicts BR BR BR when the lightest neutrino
mass is below 0.01 eV, while the inverted hierarchy predicts BR BR BR.
By precise measurement of BR, we are hopefully to probe the
lightest neutrino mass and the atmospheric mixing angle . Through
the detailed simulation of the dilepton signature and corresponding
backgrounds, we find that the 3 TeV CLIC could discover
GeV for NH and GeV for IH. Meanwhile, the future 100 TeV
FCC-hh collider could probe GeV for NH and
GeV for IH.Comment: 18 pages, 9 figure
Chromatographic determination of siphonodin content: A rapid and simple strategy for discriminating between Hemsleya omeiensis and other sources of Xuedan
Purpose: To develop a rapid and simple siphonodin content-based high performance liquid chromatography (HPLC) method to distinguish Hemsleya omeiensis from other sources of xuedan.
Methods: Siphonodin was isolated from Hemsleya omeiensis and identified by x-ray crystallographic analysis. An optimized HPLC method was applied for the determination of siphonodin contents of H. omeiensis, H. dolichocarpa and H. gigantha.
Results: Siphonodin was successfully separated by the optimized HPLC method in < 10 min, and the results of validation showed that the HPLC method was stable and very accurate for the quantification of siphonodin. The mean content of siphonodin in 10 batches of H. omeiensis was 3.78 mg/g, but the compound was not detectable in H. dolichocarpa and H. gigantha using the developed HPLC method.
Conclusion: These results indicate that the developed HPLC method is suitable for distinguishing H. omeiensis from other sources of xuedan
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 Aβ<sub>42 </sub>levels 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
Desensitizing Mitochondrial Permeability Transition by ERK-Cyclophilin D Axis Contributes to the Neuroprotective Effect of Gallic Acid against Cerebral Ischemia/Reperfusion Injury
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