Research progress of natural product evodiamine-based antitumor drug design strategies / 药学学报

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Biomechanical Analysis and Optimization of Minimally Invasive Pelvic Internal Fixation / 医用生物力学

Objective By comparing biomechanical properties of two-screw rod and three-screw rod for fixing pelvic fracture, the difference in mechanical effects of different screw rod fixation positions in pelvic minimally invasive surgery was studied.Methods The mechanical models of pelvis fixed by two-screw rod and three-screw rod were established, and biomechanical characteristics of the pelvis during standing on both legs, during single-legged standing on healthy side or affected side, as well as in sitting posture were compared and analyzed by finite element simulation, and the fixation effect of three-screw rod was verified by clinical experiments.Results Both fixation methods could restore mechanical transmission of the pelvis. But for three-screw rod fixation, the stress on both sides of the pelvis was more balanced, and the displacement of the whole body and fracture surface was also lower during single-legged standing.Conclusions The three-screw rod fixation has an excellent effect in stability, which is more beneficial for fracture recovery.

Design, synthesis and activity evaluation of protein arginine methyltransferase 5 inhibitor / 药学学报

Protein arginine methyltransferase 5 (PRMT5) is an important type II human methyltransferase. It catalyzes the symmetrical double-methylation of many histones and non-histones, and it is highly expressed in many kinds of tumors. PRMT5 has been proven to be a potential new target for cancer treatment. Based on the reported crystal complex of EPZ015666 with PRMT5, a series of new compounds was designed using GSK3326595 (EPZ015938) as the lead compound and using the conformational restriction approach. We found that compounds B8 and the C series of derivatives displayed enzyme inhibitory activity comparable to that of GSK3326595. Compounds C3 and C4 showed poor permeability in Caco-2 cells, and that might be one of the reasons for their poor anti-proliferative activity against Z-138 cells. These data provide insights for further structural optimization.

Application of a conformational restriction strategy in drug design / 中国药科大学学报

@#Conformational restriction has become one of the important strategies for modification and optimization of lead compounds in structure-based drug design. In this review, we select some recent practical examples from literature to present applications of conformational restriction in structure-based drug design. By introducing fused rings, macrocycles, spiral rings, cyclopropyl groups, bridging rings, methyl groups into molecules, we can find that the conformational restriction strategy is widely used in improving pharmacokinetic properties, enhancing the activity and selectivity, and increasing the novelty of compounds. By using these conformational restriction strategies, the drug-like properties of lead compounds can be significantly improved. This paper can help to provide theoretical guidance and practical experience for innovation in drug design and development.

Investigation and analysis of specialty categories in independent medical universities in Liaoning Province / 中华医学教育探索杂志

Using specialty and university as two statistical units,the author analyzes specialty categories,specialty composition,and the number of the disciplines established by seven independent medical universities,and indicates that in those surveyed medical universities,there is a sweeping trend of specialty diversity and generalization of non-medical specialties that most of them however have no relation with medical science and pharmacy.The author also displays negative effects of the generalization of non-medical specialties,especially on the development of medical universities,and comes up with some corresponding strategies to improve specialty setup.

Modelos computacionales de diferenciación y adaptación ósea / Computational models of bone differentiation and adaptation

Se realizó una revisión de los modelos computaciones de diferenciación y adaptación ósea existentes, haciendo énfasis en el desarrollo alcanzado en esta área durante los últimos años. El estudio del tejido óseo ha venido en aumento en las últimas décadas gracias al renacimiento de la mecanobiología, cuyo paradigma principal es la influencia que tienen las cargas mecánicas sobre el desarrollo, adaptación y mantenimiento de los tejidos. El objetivo principal del trabajo es resaltar la importancia de la mecanobiología computacional en el modelado del tejido óseo y la necesidad de seguir desarrollando la mecanobiología experimental para poder medir con exactitud las propiedades de los tejidos y las características celulares de mayor sensibilidad en los modelos computacionales

Authors review the available computational models of bone differentiation and adaptation, emphasizing on the development achieved in this area during pas years. The bone tissue study has increased in past decades due to rebirth of mechanobiology, whose main paradigm is the influence of mechanical loads on the tissues development, adaptation and maintenance. The major objective of present paper is to emphasize la significance of computational mechanobiology in the bone tissue modeling and the need to keep on developing the experimental mechanobiology to measure accurately the tissues properties and the more sensible cellular features of computational models

Projeto de caixa de madeira para manga (Mangifera Indica L. ) / Project of wooden boxes for mangoes (Mangifera Indica L. )

As perdas de produtos hortícolas no Brasil são significativas e dentre as causas cita-se o uso de caixas inadequadas e ausência da cadeia do frio. Propõe-se um método de projeto de caixas, baseado em simulação computacional, otimização e validação experimental, minimizando o volume de madeira, associado a aspectos estruturais, ergonômicos e distribuição da área de aberturas. Foram projetadose construídos três protótipos de caixas (ripas retas com diferentes configurações e área efetiva de abertura de 54% e 36%). A eficiência do resfriamento de mangas variedade Tommy Atkins (Mangifera Indica L.), foi avaliada determinando o tempo de resfriamento, acondicionando as frutas nas caixas de madeira desenvolvidas e de papelão usadas comercialmente, resfriadas com ar forçado à temperatura de 6ºC e umidade relativa média de 85,4±2,1%. Foi aplicado o Método de Elementos Finitos, para dimensionamento e otimização estrutural do modelo com melhor comportamento durante o resfriamento. Todas as caixas de madeira foram submetidas a ensaios de vibração, por duas horas (freqüência de 20 Hz). Não houve diferença significativa no tempo de resfriamento das frutas nas caixas de madeira (38,00±1,70 min), no entanto houve diferença significativa nas caixas de papelão (82,74±29,58 min). O modelo submetido à otimização estrutural (6% área efetiva e duas ripas laterais) teve diminuição de volume de 60% e 83% de redução da seção transversal das colunas, com relação às condições iniciais. Não houve incidência de danos de mecânicos nas frutas após a vibração. A simulação computacional e estrutural pode ser ferramenta de apoio para desenvolver projetos de caixas, com grande aproximação, atendendo a critérios geométricos, ergonômicos e térmicos.

Losses of horticulture product in Brazil are significant and among the main causes are the use of inappropriate boxes and the absence of a cold chain. A project for boxes is proposed, based on computer simulations, optimization and experimental validation, trying to minimize the amount of wood associated with structural and ergonomic aspects and the effective area of the openings. Three box prototypes were designed and built using straight laths with different configurations and areas of openings (54% and 36%). The cooling efficiency of Tommy Atkins mango (Mangifera Indica L.) was evaluated by determining the cooling time for fruit packed in the wood models and packed in the commercially used cardboard boxes, submitted to cooling in a forced-air system, at a temperature of 6ºC and average relative humidity of 85.4±2.1%. The Finite Element Method was applied, for the dimensioning and structural optimization of the model with the best behavior in relation to cooling. All wooden boxes with fruit underwent vibration testing for two hours (20 Hz). There was no significant difference in average cooling time in the wooden boxes (36.08±1.44 min); however, thedifference was significant in comparison to the cardboard boxes (82.63±29.64 min). In the model chosen for structural optimization (36% effective area of openings and two side laths), the reduction in total volume of material was 60% and 83% in the cross sectionof the columns. There was no indication of mechanical damage in the fruit after undergoing the vibration test. Computer simulations and structural study may be used as a support tool for developing projects for boxes, with geometric, ergonomic and thermal criteria.