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1.
Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) in particulate matter that has a diameter of ≤2.5 μm (PM2.5). Studies have demonstrated that BaP exposure causes oocyte meiotic arrest in mice. However, whether BaP exposure also affects oocyte maturation in offspring remains unclear. To test this, female mice were administered BaP before pregnancy to generate BaP-exposed offspring. Our findings showed that BaP exposure reduced the in vitro maturation and increased the abnormalities of meiotic apparatus in offspring oocytes. In addition, BaP exposure reduced the mitochondrial content and intracellular ATP generation, induced early apoptosis, increased reactive oxidative species accumulation and the genomic DNA 5-methylcytosine (5mc) level in offspring oocytes. Along with the abovementioned defective parameters, maternal BaP exposure further compromised the embryo developmental competence of offspring oocytes. In summary, our study demonstrated that maternal BaP exposure compromised offspring oocyte maturation and quality. 相似文献
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3.
双环[1.1.1]戊烷(BCP)是一种具有三维立体结构的桥环骨架,其作为苯环、叔丁基和炔烃的生物电子等排体,已经在药物化学领域得到广泛的应用。随着BCP应用范围的扩大,BCP及其衍生物的合成日益成为研究的热点。本文对BCP衍生物的主要合成策略和方法进行总结,旨在为新药研发人员提供参考。 相似文献
4.
《药学学报(英文版)》2020,10(7):1294-1308
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents. 相似文献
5.
Samira Marín-Romero Teresa Elías-Hernández María Isabel Asensio-Cruz Rocío Ortega-Rivera Raquel Morillo-Guerrero Javier Toral Emilio Montero Verónica Sánchez Elena Arellano José María Sánchez-Díaz Macarena Real-Domínguez Remedios Otero-Candelera Luis Jara-Palomares 《Archivos de bronconeumología》2019,55(12):619-626
IntroductionScales for predicting venous thromboembolism (VTE) recurrence are useful for deciding the duration of the anticoagulant treatment. Although there are several scales, the most appropriate for our setting has not been identified. For this reason, we aimed to validate the DASH prediction score and the Vienna nomogram at 12 months.MethodsThis was a retrospective study of unselected consecutive VTE patients seen between 2006 and 2014. We compared the ability of the DASH score and the Vienna nomogram to predict recurrences of VTE. The validation was performed by stratifying patients as low-risk or high-risk, according to each scale (discrimination) and comparing the observed recurrence with the expected rate (calibration).ResultsOf 353 patients evaluated, 195 were analyzed, with an average age of 53.5 ± 19 years. There were 21 recurrences in 1 year (10.8%, 95% CI: 6.8%-16%). According to the DASH score, 42% were classified as low risk, and the rate of VTE recurrence in this group was 4.9% (95% CI: 1.3%-12%) vs. the high-risk group that was 15% (95% CI: 9%-23%) (p <.05). According to the Vienna nomogram, 30% were classified as low risk, and the rate of VTE recurrence in the low risk group vs. the high risk group was 4.2% (95% CI:0.5%-14%) vs. 16.2% (95% CI: 9.9%-24.4%) (p <.05).ConclusionsOur study validates the DASH score and the Vienna nomogram in our population. The DASH prediction score may be the most advisable, both because of its simplicity and its ability to identify more low-risk patients than the Vienna nomogram (42% vs. 30%). 相似文献
6.
Hend Kothayer Samy M. Ibrahim Moustafa K. Soltan Samar Rezq Shireen S. Mahmoud 《Drug development research》2019,80(3):343-352
In light of the pharmacophoric structural requirements for achieving anticonvulsant activity, a series of N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)benzamide (4a-g) and N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)-2-phenylacetamide (4h-n) derivatives were synthesized in two steps starting from the reaction of N-methyl isatoic anhydride with the appropriate hydrazide and followed by condensation with the appropriate aldehyde. The anticonvulsant activities of the synthesized compounds were evaluated according to the anticonvulsant drug development (ADD) programme protocol. Among the synthesized compounds, 4n showed promising activity in both the maximal electroshock (MES) and pentylenetetrazole (PTZ) tests with median effective dose (ED50) values of 40.7 and 6 mg/kg, respectively. The six most promising derivatives, 4b , 4a , 4c , 4f , 4j , and 4i , showed very low ED50 values in the PTZ test (3.1, 4.96, 8.68, 9.89, 12, and 13.53 mg/kg, respectively). All the tested compounds showed no to low neurotoxicity in the rotarod test with a wide therapeutic index. Docking studies of compound 4n suggested that GABAA binding could be the mechanism of action of these derivatives. The in silico drug likeliness parameters indicated that none of the designed compounds violate Lipinski's rule of five and that they are able to cross the blood–brain barrier.
相似文献
Hit, Lead & Candidate Discovery |
7.
《Research in social & administrative pharmacy》2020,16(11):1597-1601
Disseminating research findings from global health collaborations is essential to advancing science. However, there are a number of ethical considerations and potential challenges to address to ensure thoughtful and non-exploitative reporting. The factors include the benefits and risks to publication, authorship criteria or values, and the accessibility of forums or journals in which to pursue publication. This paper provides commentary related to planning for writing, communicating intentions to publish, obtaining permissions to publish, risks in internationally collaborative work, authorship principles, and journal selection. Authors' and editors’ knowledge of experienced individuals from both pharmacy literature, medical fields, and general publications is incorporated to provide an assessment of risks and benefits of publication of international global health research. 相似文献
8.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(4):339-343
Condensation of thiourea 1 with diethyl malonate 2 in the presence of sodium methoxide furnished 4,6‐dihydroxy‐2‐mercaptopyrimidine 3 . Compound 3 on methylation with diazomethane followed by oxidation with H5IO6/CrO3 in ethyl acetate gave 4,6‐dimethoxy‐2‐methylsulphonylpyrimidine 5 . Compound 5 on condensation with 2‐mercapto‐6‐chlorobenzoic acid in the presence of a phase transfer catalyst, tetrabutylammonium bromide and sodium carbonate gave the title compound – pyrithiobac‐sodium 6 with an overall yield of > 35% starting from thiourea. Following the above standardized procedure, using [14C]‐thiourea in lieu of thiourea, 14C labelled product 6 , was synthesized with an overall radiochemical yield > 30% (with respect to [14C]‐thiourea) for further evaluations of environmental fate of 6 , in soils and plants. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
9.
Jen auo Hirschberg 《Early child development and care》1990,65(1):57-69
During a period of twenty years [1969-1988] the author has observed 614 cases of congenital malformations and noninflammatory diseases of the larynx in infants and young children, Budapest. He summarizes the most characteristic symptoms of laryngeal pathology in infants, and discusses the diagnostic possibilities. Among the latter, spectrographic analyses complemented by auditory evaluation of pathological cry and different breathing noises play an important role. Based on his investigation author differentiates 20 kinds of pathological crying sounds and 4 basic forms of stridor. He describes the acoustic attributes of different pathological sound phenomena and summarizes characteristic voice changes. 相似文献
10.
《Journal of labelled compounds & radiopharmaceuticals》2005,48(9):693-700
[(1R)‐endo]‐(+)‐3‐bromocamphor was dehalogenated with tritium gas to [3‐3H]camphor and via [3‐3H]phenylborneol converted to [3‐3H]deramciclane isolated as the fumarate salt (specific activity 51.8 GBq/mmol). This three step synthesis from [3‐3H]camphor gave an overall yield of 22%. Benzyloxy‐acetic acid methyl ester was reduced with sodium‐borotritide to 2‐benzyloxy‐ethanol‐[1‐3H], and through a four step procedure was converted to 2‐dimethylaminoethyl‐[2‐3H] chloride. The latter was condensed with the sodium derivative of 2‐phenylborneol giving rise to [2‐dimethylamino‐[2‐3H]ethoxy]deramciclane isolated as the fumarate (specific activity 8.177 GBq/mmol). This six step synthesis from [3H]NaBH4 gave an overall yield of 6%. Copyright © 2005 John Wiley & Sons, Ltd. 相似文献