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【Objective】 To investigate the effects of WM-3835, a histone acetyltransferase KAT7 (KAT7) inhibitor, on the proliferation and migration of bladder cancer cells and to explore the possible mechanism. 【Methods】 Human ureteral epithelial immortalized cell line SV-HUC-1, and bladder cancer cell lines UM-UC-3 and T24 were treated with different concentrations of WM-3835 (0, 10, 20, 30, 40 μmol/L). After 48 hours, the effects of WM-3835 on the proliferation, cell cycle distribution and migration of cells were detected with MTT assay, flow cytometry, scratch and Transwell assay, respectively. The expressions of cyclin D1 (cyclin D1), proliferating nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP9) and neurocadherin (N-cadherin) were detected with Western blotting and real-time quantitative PCR. 【Results】 WM-3835 significantly inhibited the proli-feration of bladder cancer cells in a dose-dependent manner. After treatment with WM-3835, the cycle of UM-UC-3 and T24 cells were blocked in the G0/G1 phase, the proliferation was effectively inhibited, and the migration was significantly wea-kened. The expressions of cyclin-D1, PCNA, MMP9 and N-cadherin were down-regulated. 【Conclusion】 WM-3835 can inhibit the proliferation and migration of bladder cancer cells, and has the potential as a chemotherapeutic agent for bladder cancer.
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OBJECTIVE:To optimize the formulation of Methotrexate thermosensitive hydrogels,and to study the in vitro re-lease property of it. METHODS:Taking PLGA-PEG-PLGA as matrix and mannitol as viscosity modifiers,Methotrexate thermosen-sitive hydrogels were prepared. Using the absolute value of the deviation of gelation temperature between 35 ℃,its formulation was optimized by orthogonal test using the concentrations of PLGA-PEG-PLGA,methotrexate and mannitol as factors. The dialysis bag method was used to investigate accumulative release rate of Methotrexate thermosensitive hydrogels and methotrexate solution within 336 h in vitro. RESULTS:The optimal formulation was as PLGA-PEG-PLGA of 20%,methotrexate of 0.10% and mannitol of 0.10%;gelation temperature were 35.1,35.0,35.0℃. The average drug-loading rate was more than 90%. 12 d accumulative re-lease rate was more than 90%(r=3). Methotrexate solution has been substantially completely relased within 240 h. CONCLU-SIONS:Methotrexate thermosensitive hydrogels with sustained-release are prepared successfully,and the preparation technology is simple and practical.
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Objective:To investigate the radiosensitizing effect of three flavonoids on ovarian cancer SKOV3 cells under hypoxia. Methods:The SKOV3 cells were divided into normoxic group and hypoxic group. The hypoxic SKOV3 cellular model in vitro was es-tablished and tested by measuring the expression profile of HIF-1αprotein in SKOV3 cells. Colony-forming assay was used to detect the radiosensitivity of normoxic and hypoxic SKOV3 cells. The cytotoxicity and radiosensitizing effects of flavonoids were evaluated on the basis of cell death and MTT assay. Results:The Western blot results showed that the gray intensity ratio of HIF-1α/β-Actin in hypoxia group was significantly higher than that in normoxia group (1. 068>0. 117). Radiosensitivity of hypoxic SKOV3 cells in hypoxia group was significantly lower than that in normoxia group. The survival rate of SKOV3 cells was decreased with the increase of concentration. When the concentration was increased, D0 and Dqin chrysin group and quercetin group were significantly decreased (P0. 05). The overall radiobiological parameters of hypoxia group were higher than those of normoxia group. Conclusion: Hypoxia can induce the expression of HIF-1α in SKOV3 cells, which results in the decrease of radiosensitivity. Chrysin and quercetin can enhance the radiosensitivity of SKOV3 cells, and the enhancement is significant under hypoxia, while breviscapine is without such effect. The radiosensitizing effect may be achieved by the level decrease of HIF-1α in SKOV3 cells and inhibition of DNA damage repair.
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Triamcinolone acetonide is one of adrenocorticotropic hormones. Its anti-inflammatory and anti-allergic effects are strong and lasting. However, due to its poor water solubility and systemic side effects, researchers try to transform and create its new formula constantly. The paper reviewed the research progress in new formula of triamcinolone acetonide at home and abroad in recent years, including solid dosage forms, emulsion, particle dispersion system and the other new formula which have been researched in or-der to provide information for the improvement of bioavailability and safety.
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Objective To prepare triamcinolone acetonide acetate(TAA)thermosensitive hydrogel for intra-articular injection,and to investigate its release in vitro. Methods TAA suspending thermosensitive hydrogel was prepared by using poly lactic-co-glycolic acid(PLGA)-polyethylene glycol(PEG)-PLGA as gel matrices,xanthan gum as suspending agent and NaCl as flocculant. It was evaluated preliminarily by determining its contents and its in vitro release. Results The best compositions for preparation of TAA suspending thermosensitive hydrogel were 25% PLGA-PEG-PLGA,0.05% xanthan gum, 0.9% NaCl and 4 mg·mL-1 TAA.The gelation temperature was 35.3 ℃ .The average recovery was(98.98±0.31)%. By the method of membraneless dissolution,the accumulative drug release was up to 83. 31% at 16 days. The drug release followed Ritger-Peppas methematical model. Conclusion The TAA thermosensitive hydrogel with obviously sustained release is expected to become a new drug delivery system for intra-articular injection.
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Objective To investigate the characteristics of the objective sleep disturbances in Parkinson' s disease (PD) and the factors related to it.Methods One hundred and one PD patients and 90 age- and sex- matched controls underwent a video-polysomnography.The sleep parameters and its related factors in two groups were analyzed.Results Sleep latency was not statistically different in comparing two groups.PD patients had a higher percentage of non-rapid eye movement( non-REM ) sleep stage 1 and a lower percentage of non-REM sleep stage 2 compared with controls ( 27.9 ± 1 7.8 vs 21.2 ± 11.7,t =3.034,P =0.003 ;47.8 ± 17.4 vs 54.7 + 12.9,t =- 3.043,P =0.003 ).Reduced sleep efficiency,decreased the proportion of slow wave sleep and REM sleep,increased awake time and longer REM sleep latency occurred in PD patients.There were no significant differences of these above parameters.Some sleep parameters in PD patients were correlated with advancing age,the severity of PD,and the degree of depression.The index of periodic leg movements in sleep (PLMSI) of 41 PD patients (40.6％ ) was more than 15.These PD patients didn' t complain corresponding symptoms about their legs.The PLMSI in PD patients were significantly higher than the controls.PLMSI increased with aging in the PD group( r =0.261,P ＜0.01 ).PD patients didn' t suffer significantly lower apnea- hypopnea index and oxygen desaturation index.The lowest SPO2 ( L-SPO2 ) increased in the PD group.REM sleep without atonia occurred in 83 patients (82.2％) with PD.Thirty-eight patients (37.6％) were diagnosed with REM sleep behavior disorder (RBD).The incidences of REM without atonia and RBD in the PD group were significantly higher than in the control s(0 and 8 patients (8.9％),x2 =42.271,102.480; both P ＜ 0.01 ).Conclusions The sleep parameters in PD patients are changed.For PD patients,there is no difficulty in falling asleep.The PD patients also have sleep structure disorder and difficulty in maintaining sleep.The sleep parameters are correlated with advancing age,the severity of PD,and the degree of depression in PD.PLMS don' t lead to sleep disturbances in PD patients.The blood oxygen saturation don' t decrease severely when PD patients suffer apnea or hypopnea.RBD occur more frequently in PD patients.
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Sleep apnea syndrome (SAS) is an independent risk factor for atherosclerosis and stroke. Studies have shown that the incidence of SAS increases significantly after stroke.This article reviews the mechanism of atherosclerosis caused by SAS and the characteristics and research progress of sleep apnea after stroke.
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Objective To analyze the characteristics and influencing factors of sleep disorders and nocturnal hypoxemia of patients with different degrees of obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods Four hundred and twenty-five patients with snoring were scored by Epworth Sleepiness Scale ( ESS), and monitored by polysomnography (PSG). The possible correlations between sleep structure, hypoxia parameters, ESS and clinical features were analyzed and compared in those patients. Results Four hundred and twenty-five patients were divided into 4 groups according to the apnea-hypopnea index (AHI). There were 65 primary snoring patients (15.3%) and 360 OSAHS patients (84. 7% ) including 187 patients (44. 0% ) in severe OSAHS group. ESS was increased as aggravation of OSAHS. There were significant statistical differences in ESS among each group. Compared with primary snoring group, sleep efficiency, NREM1 + 2, oxygen desaturation index ( ODI), time with pulse oxygen saturation below 90% (T(SpO2 <90% ) ) were significantly higher in the OSAHS groups, and NREM3 +4, lowest pulse oxygen saturation level ( LSpO2 ) were lower. ESS was correlated positively with AHI (r= 0. 474,P <0. 01 ). They were both correlated positively with ODI, T (SpO2 <90% ) and NREM1 + 2( ESSr =0. 392, 0. 356,0. 194;AHI r = 0. 714, O. 682, 0. 365, all P < 0. 01 ), and correlated negatively with LSpO2, NREM3 + 4 ( ESS r = - 0. 414, - 0. 196; AHI r = - 0. 740, - 0. 385, both P < 0. 01 ). LSpO2, ODI and T (SpO2 < 90% ) were the primary influencing factors. Common clinical presentations and subjective symptoms were presented including daytime sleepiness, impaired memory, fatigue, dry mouth, oppressive wake and morning headache, etc. Percentage of individuals with daytime sleepiness in the severe OSAHS group was 73. 3% (137/187). These had serious impact on the patients' quality of life, leading to difficulty concentrating, poor memory and cognitive impairment. Conclusions Sleep disorders are found in the patients with different degrees of OSAHS. The excessive daytime sleepiness interrelated partly with the structure of sleep, and totally with hypoxia parameters. The more severity the patients have, the more nocturnal hypoxia, sleep disorders and higher ESS are found.