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Objective: To investigate the effects of IMPX977 on long term potentiation (LTP) at Schaffer collateral-CA1 synapses in vitro and on methyl CpG binding protein 2 (Mecp2) expression in mice cortex and hippocampus. Methods: Thirty-two C57BL/6 mice were randomly divided into four groups: control, olive oil (vehicle), IMPX977 low (5 mg/kg) and high (15 mg/kg) groups. Mice were administrated every other day orally for two weeks. Extracellular recording technique in vitro was used to record the effects of IMPX977 on Schaffer collateral-CA1 LTP pathway in acute mice hippocampal slices. The Mecp2 protein expression level was detected by Western blotting. Results: Compared to the control group, vehicle did not alter the synaptic transmission in Schaffer collateral-CA1 synapses, however, IMPX977 at concentrations of 5 mg/kg and 15 mg/kg significantly enhanced fEPSP (field excitatory postsynaptic potential) slope in Schaffer collateral-CA1 pathway to (179.6 ± 17.8)% and (191.4 ± 21.4)%, individually 60 min after HFS, IMPX977 improved LTP induction significantly at Schaffer collateral-CA1 pathway at least. Also, IMPX977 significantly elevated MeCP2 protein level in cortex. Conclusion: The effects of IMPX977 on synaptic transmission and Mecp2 protein expression provided convincing evidence that IMPX977 could be promising new drug candidates for Rett syndrome treatment.
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Fufang Niuhuang Xiaoyan capsule was a classical compound prescription with the efficacy of heat-clearing, detoxification, sedation and anti-inflammation, with cinnabaris as one of its active ingredients. The study focuses on the pharmacokinetics of mercury in rats after oral administration of cinnabaris and Fufang Niuhuang Xiaoyan capsule, in order to explore the effect of combined traditional Chinese medicines on mercury metabolism. In this study, the method of nitric-perchloric acid digestion system coupled with cold atomic-atomic fluorescence spectroscopy (CV-AFS) was adopted to accurately determine mercury in whole blood of rats. Fufang Niuhueng Xiaoyan capsule had three dose schemes of oral administration, namely equivalent clinical dose, 3 times of equivalent clinical dose and 10 times of equivalent clinical dose; And the doses of oral administration of cinnabaris was calculated according to that of Fufang Niuhuang Xiaoyan capsule. SPF grade healthy SD rats were fasted overnight before the oral administration with cinnabaris suspension (or Fufang Niuhuang Xiaoyan capsule suspension). After oral administration of different doses of cinnabaris, no obvious changes in tmax and MRT were observed, while Cmax/dose, AUC0-48 h/dose and AUC0-∞/dose decreased with the increase in dose, indicating that total mercury absorption in body was declining. As the dose increased, Ke, CL/F decreased, and t1/2 increased, indicating that the elimination slowed down, and mercury metabolism showed non-linear dynamic characteristics within a certain range of dose (22-220 mg•kg⁻¹). The total mercury metabolism in the whole blood of rats after oral administration with different doses of Fufang Niuhuang Xiaoyan capsule also showed non-linear dynamic characteristics. The results were correlated with the low solubility of cinnabaris in the body. Compared with cinnabaris, Fufang Niuhuang Xiaoyan capsule showed no obvious changes in V/F and MRT, while Ke, CL/F, tmax decreased, and t1/2, Cmax/dose, AUC0-48 h/dose, AUC0-∞/dose increased significantly. The results showed that Fufang Niuhuang Xiaoyan capsule accelerated absorption, slowed down elimination and improved the total absorption of mercury in the whole blood, indicating that Fufang Niuhuang Xiaoyan capsule may contain components for promoting absorption and alleviating elimination of mercury. Fufang Niuhuang Xiaoyan capsule had an impact on the pharmacokinetics of cinnabaris, and long-term administration of cinnabaris (Fufang Niuhuang Xiaoyan capsule) was possible to cause accumulation of mercury in the body. This study could explain changes in efficacy of Fufang Niuhuang Xiaoyan capsule, evaluate the rationality of compound medicines containing toxic elements and provide scientific basis for the rational and safe use of Fufang Niuhuang Xiaoyan capsule.
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PURPOSE: Insufficient sensitivity and specificity prevent the use of most existing biomarkers for early detection of breast cancer. Recently, it was reported that serum microRNAs (miRNAs) may be potential biomarkers in many cancer diseases. In this study, we investigated whether serum levels of 5 miRNAs including miR-21, miR-125b, miR-145, miR-155, and miR-365 could discriminate breast cancer patients and healthy controls. METHODS: Serum levels of miRNAs were measured by using quantitative real-time polymerase chain reaction in 99 breast cancer patients and 21 healthy controls. The abundance change of serum miRNAs were also evaluated following surgical resection in 20 breast cancer patients. Receiver operating characteristic (ROC) curve analysis was performed to assess the sensitivity and specificity of miRNAs as diagnostic biomarkers. RESULTS: Serum levels of miR-21 and miR-155 was significantly higher, while miR-365 was significantly lower in breast cancer as compared with healthy controls. The serum levels of miR-21 and miR-155 significantly decreased following surgical resection. Additionally, the serum level of miR-155 at stages I and II was significantly higher compared to stage III. The serum miR-145 level was remarkably higher in progesterone receptor (PR)-positive patients than PR-negative. The positivity of miR-21, miR-155, and miR-365 was high compared to CA 153 and CEA in breast cancer. ROC curve analyses of a combination of miR-21, miR-155, and miR-365 yielded much higher area under curve and enhanced sensitivity and specificity in comparison to each miRNA alone. CONCLUSION: The combination of serum miR-21/miR-155/miR-365 may potentially serve as a sensitive and specific biomarker that enables differentiation of breast cancer from healthy controls.
Subject(s)
Humans , Area Under Curve , Biomarkers , Breast Neoplasms , Breast , MicroRNAs , Real-Time Polymerase Chain Reaction , Receptors, Progesterone , ROC Curve , Sensitivity and SpecificityABSTRACT
<p><b>AIM</b>(+/-) Ibuprofen sugar derivatives were prepared in order to decrease side-effects and increase bioavailability of (+/-) ibuprofen.</p><p><b>METHODS</b>The synthesis of derivatives were performed using 1,2:3, 4-di-O-isopropylidene-beta-D-galactopyranose, 1,3,4,5-tetra-O-acetyl-2-deoxy-2-amino-beta-D-gluctopyranose, 3,4 6-tri-O-acetyl-2-deoxy-2-N-acetyl-beta-D-gluctosylamine and 2,3,6,2',3',4',6'-hepta-O-acetyl-beta-D-lactosylamine as glycosyl donors, respectively. Target products (4, 7, 12a, 12b, 13) were obtained after deprotection.</p><p><b>RESULTS</b>Five compounds (4, 7, 12a, 12b, 13) were synthesized as new compounds. The structures of all objective compounds were confirmed by 1HNMR, 13CNMR, HMQC, COSY, IR and MS.</p><p><b>CONCLUSION</b>It was found that 12a showed better anti-inflammatory activity than (+/-) ibuprofen.</p>
Subject(s)
Animals , Male , Mice , Anti-Inflammatory Agents, Non-Steroidal , Therapeutic Uses , Ibuprofen , Therapeutic Uses , Inflammation , Drug Therapy , Molecular Conformation , Molecular Structure , Random AllocationABSTRACT
Objective To observe the effects of culture medium of a mn iotic cells on NO and NOS in retinal tissues of rabbits in vitro in order to pro vide a protective method for antioxidation in retina transplantation. M ethods Thirty adult healthy rabbits (30 right eyes) were divided into 3 groups. Group Ⅰ: fresh retinal tissue; group Ⅱ: routine culture medium; group Ⅲ: culture medium of amniotic cells. The retinal tissues in group Ⅱ and Ⅲ we re cultured in the corresponding culture medium for 1 week. The content of NO an d NOS in retinal tissues in the 3 groups were determined. Results Compared with group I, the content of NO and NOS of group Ⅱ increased obvio usly (t=3.821, 3.854; P0.05) . Conclusion Culture medium of amniotic cells may remove free r adicals and enhance the ability of antioxidation.
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Quaternary ammonium glucosamine conjugatewas prepared by a two step procedure.First,condensation of glucosamine hydrochloride with chloro acetic chloride in the presence of potassium bicarbonate in aqueous medium at 0℃ provided the N chloroacetyl derivative in 74% yield.Subsequent reaction of this intermediate with pyridine at 40℃ for 3 days gave the pyridinium conjugate in 71% yield.The structures of compounds were confirmed by IR,NMR spectra and element analysis.
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Basic aluminium 6 ? (carboxylmethyl) chitosan was prepared by reacting the solution of 6 ? (carb?xylmethyl) chitosan in water with basic aluminium chloride 〔Al(OH) 2Cl〕. The structure of product was confirmed by IR and atomic absoption spectroscopy.
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Chitosan and it's derivatives have good biologic and particular physical and chemical properties. They have a wide applied foreground on drug preparations. This study introduced the recent advances of them based on widely researching the information and the actual works, and provided reference for the study of oral drug preparations.
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Reaction of chitosan with glucose, galactose and lactose was performed in lactic acid MeOH to give corresponding schiff's base derivatives, the following reduction was carried out in the presence of sodium cyanoborohydride to prepare branched chain water soluble chitosan derivatives. The structure of derivatives were Confirmed by 1 HNMR and 13 CNMR.
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N alkylated Partially deacetylated chitin(DAC 85)was prepared via reductive N alkylation in aceques MeOH with lauraldehyde.Further,O carboxymethlation of N alkylatedchitosan was performed in 55% NaOH with carboxymethy chloride.A new type amphiphilic chitosan derivative was achieved.Elementary analysis and IR spectrume was performed to study the characterization of the chitosan derivative.