Paeoniflorin ameliorates oxidase stress in Glutamate-stimulated SY5Y and prenatally stressed female offspring through Nrf2/HO-1 signaling pathway.

BACKGROUND: Prenatal stress (PS) can cause brain retardation, reduce the learning and memory ability of the offspring and significantly increase the incidence of depression in offspring. Paeoniflorin (PF), a kind of monoterpenoid glycoside, is one of the main active ingredients of Chinese Medicine Paeonia lactiflora Pall, has anti-inflammation and potential neuroprotective effects. However, few reports have shown that the neuroprotective effects of PF are exerted through ameliorating Glutamate toxicity in vivo and in vitro. METHODS: Here, we used a prenatal restraint stress model and Glu-induced excitotoxic neurotoxicity in SH-SY5Y cells to study the effects of PF. RESULTS: Our results showed that PF can ameliorate learning and memory impairments and increases the density of hippocampal neurons, typical Golgi-positive pyramidal cells, and neuronal Neurogranin (Ng) expression in PS rat offspring. Furthermore, PF can significantly up-regulate the decrease of Glu-induced SH-SY5Y cell viability. At the same time, PF can significantly reduce apoptosis, ROS, NO levels, and intracellular Ca2+ concentration, and significantly inhibit the increase of mitochondrial membrane potential. Besides, PF significantly increased the expression of Nrf2 and iNOS, decreased p-JNK/JNK, p-P38/P38, Bax/Bcl-2, active-caspase-3, and active-caspase-9. CONCLUSIONS: Our results demonstrate that PF may be an effective treatment in preventing the development of PS-induced learning and memory impairment and have therapeutic potential in Glu-related neurological diseases.

Neuroprotective effects of aucubin on hydrogen peroxide-induced toxicity in human neuroblastoma SH-SY5Y cells via the Nrf2/HO-1 pathway.

BACKGROUND: When redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis. PURPOSE: The present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (H2O2)-induced injury in SH-SY5Y cells in vitro. METHODS: SH-SY5Y cells were simultaneously treated with AU and H2O2 for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry. RESULTS: The results showed that AU can significantly increase the H2O2-induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that H2O2 stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In H2O2-induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways. CONCLUSION: These results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways.

Icariin reduces Glu-induced excitatory neurotoxicity via antioxidative and antiapoptotic pathways in SH-SY5Y cells.

Excessive glutamate (Glu) can lead to significant effects on neural cells through the generation of neurotoxic or excitotoxic cascades. Icariin (ICA) is a main active ingredient of Chinese Medicine Berberidaceae epimedium L., and has many biological activities, such as antiinflammation, antioxidative stress, and anti-depression. This study aims to evaluate the effect of ICA on Glu-induced excitatory neurotoxicity of SH-SY5Y cells. The cell viability assay was evaluated by the CCK-8 assay. The apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential were assessed by flow cytometry. Intracellular Ca2+ concentration was determined by using the fluorescent probe Fluo-3. Protein expression was detected by western blotting analysis. ICA can significantly enhance the SH-SY5Y cell viability reduced by Glu. At the same time, ICA can significantly reduce apoptosis, ROS, nitric oxide (NO) levels, and intracellular Ca2+ concentration, and significantly inhibit the increase of mitochondrial membrane potential. In addition, ICA significantly increased the expression of P47phox and iNOS, decreased p-JNK/JNK, p-P38/P38, Bax/Bcl-2, active caspase-3, and active caspase-9. These results indicate that ICA may reduce the excitatory neurotoxicity of Glu-induced SH-SY5Y cells through suppression of oxidative stress and apoptotic pathways, suggesting that ICA could be a potential therapeutic candidate for neurological disorders propagated by Glu toxicity.

The first-principles and BTE investigation of phonon transport in 1T-TiSe2.

Through the first-principles density functional theory and the phonon Boltzmann transport equation, we investigated the phonon transport characteristics inside 1T-TiSe2. The calculation results of the lattice thermal conductivity (κl) show that the κl of TiSe2 is extremely low (1.28 W (m K)-1, 300 K) and decreases with the shrinkage of the sample size. Moreover, the results also prove the isotropic nature of thermal transport. By decomposing the contribution of the thermal conductivity according to the frequency, the κl of the single-layer TiSe2 is primarily attributed to the acoustic phonons and a small portion of optical phonons, with the frequency range of 0-4.5 THz. The calculation of the scattering rate further illustrates the competition of different scattering modes in this frequency range to verify the change in thermal conductivity of different sample sizes. The high scattering rate and low group velocity lead to the low thermal conductivity of the optical phonon mode in TiSe2. In addition, reducing the size of the system can significantly limit the thermal conductivity by eliminating the contribution of long mean free path phonons. When the characteristic length of the single-layer TiSe2 is about 14.92 nm, κl reduces to half. Our results also show that TiSe2 has an extremely high Grüneisen parameter (about 2.62). Further decomposition of the three-phonon scattering phase space and scattering rate demonstrates that in the range 0-4.5 THz, the absorption process is the main conversion form of phonons. We conclude that, due to the high Grüneisen parameter, the high anharmonicity in TiSe2 leads to the extremely low κl. This study provides κl related to the temperature, frequency, and MFP, and deeply discusses the phonon transport in TiSe2, which has great significance to further adjust the thermal conductivity to develop highly efficient thermoelectric materials and promote the application of devices based on TiSe2.

Fluctuation-dissipation analysis of nonequilibrium thermal transport at the hydrate dissociation interface.

Herein, a nonequilibrium molecular-dynamics simulation in an NVE ensemble was performed to investigate the spontaneous dissociation of methane-hydrate when it came in contact with liquid water. The nonequilibrium in the interface region is linked to the dissociation process of the hydrate near the interface according to the Onsager's hypothesis. The simulated thickness of the interface was found to be close to the acoustic phonon mean path of methane hydrate and agreed with the reference value. The normalized heat flow autocorrelation function was introduced to study fluctuation-dissipation in terms of the thickness and moving velocity of the interface and the Stefan number. This helped to clearly identify three distinct hydrate-decomposition regimes dominated by sensible heat, latent heat and an intrinsically unstable lattice framework. It was found that the fluctuation-dissipation theory could express the nonequilibrium nature in the front two stages before the threshold was reached, and the dissociation rate increased in the latter stage; this was different from the case of thermal-driven dissociation. The Stefan number decreased rapidly with dissociation in the initial stage and then fluctuated in the intermediate stage; this was analogous to the fluctuation characteristics of the heat flow autocorrelation function. The Stefan number effect shows that thermal dissipation drives the hydrate dissociation and correlates fluctuation to the nonequilibrium nature. It was also found that a small Stefan number was enough to break up the residual hydrate soon after the threshold was achieved. The transient interfacial thermal resistance of the interfacial region was obtained as a typical value in the range of 10-7-10-9 m2 K W-1. This justifies that fluctuation-dissipation exists in the nonequilibrium process of hydrate dissociation either in terms of heat flux, as observed in this study, or the diffusion of guest molecules, as reported in other studies.

A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy-A single-institution experience.

BACKGROUND: Management of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin-preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as "T1G3." OBJECTIVE: To evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We retrospectively reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18-70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response. RESULT: Complete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035). CONCLUSION: GC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression.

[Effects of gantry position on the accuracy of lead block localization and relative quality control methods].

BACKGROUND & OBJECTIVE: To date, the low-melting point lead blocks are commonly used as a beam modifier for the accurate three-dimensional (3D) radiotherapy in China. However, care should be taken when using blocks even though they are verified on the specified simulator or linear accelerator before treatment. This is because that those verifications are only performed under the gantry angle of 0 degree. For the oblique gantry angles, the block may shift in the tray leading to the positioning error. In this study, we explored the influence of gantry position on the accuracy of lead block localization, and the relative quality control methods were also provided. METHODS: After rotating the gantry to 90 degrees and setting the collimator angle to 0 degree on a Siemens linear accelerator, a crosshair was marked on the plastic base of the lead block fitted to the tray according to the crosshair of light field of the linear accelerator. Then the discrepancy between the base crosshair and the light crosshair was investigated for different gantry positions and collimator angles. RESULTS: There was clearance between the plastic base of the lead block and the block tray. As for some collimator angles at oblique gantry positions, the lead block shifted in the tray due to the gravity. This led to the position error of blocked radiation fields from 0 up to 3.6 mm at the isocenter plane. CONCLUSIONS: Accurately marking the crosshair on the plastic base of the lead block is an effective method of correctly fixing the lead block influenced by the plastic base as well as of double checking the accuracy of the localization of the lead block. The positioning error of oblique gantry positions can be minimized by limiting the collimator to some degrees which makes the block tray opening to the ceiling or parallel to the ground while the bisector of the restrictive angle points slanting to the ceiling (that is, the first baseline of the block tray points inclined or right to the ceiling).