Transgenic Rodent Models in Toxicological and Environmental Research: Future Perspectives

The coexistence of humans and animals has existed for centuries. Over the past decade, animal research has played a critical role in drug development and discovery. More and more diverse animals, including transgenic animals, are used in basic research than in applied research. Transgenic animals are generated using molecular genetic techniques to add functional genes, alter gene products, delete genes, insert reporter genes into regulatory sequences, replace or repair genes, and make changes in gene expression. These genetically engineered animals are unique tools for studying a wide range of biomedical issues, allowing the exhibition of specific genetic alterations in various biological systems. Over the past two decades, transgenic animal models have played a critical role in improving our understanding of gene regulation and function in biological systems and human disease. This review article aims to highlight the role of transgenic animals in pharmacological, toxicological, and environmental research. The review accounts for various types of transgenic animals and their appropriateness in multiple types of studies.

Research progress of clinical application of human fibrinogen / 中国输血杂志

In bleeding events caused by various reasons, coagulation dysfunction due to massive consumption or loss of coagulation factors is often life-threatening. In recent years, medical evidence of using human fibrinogen concentrate to prevent or treat bleeding has emerged, providing more options for clinical treatment of bleeding. In this paper, the stability, pharmacokinetics and safety of human fibrinogen, as well as the latest advances in its clinical application in obstetrics, cardiac surgery and traumatic massive hemorrhage were summarized, and new reasonable suggestions for clinical application of human fibrinogen were also put forward.

Dalbergia ecastaphyllum leaf extracts: in vitro inhibitory potential against enzymes related to metabolic syndrome, inflammation and neurodegenerative diseases

For the first time, the anti-hemolytic activity and the enzyme inhibitory activities of Dalbergia ecastaphyllum leaves extracts were tested against α-amylase, α-glucosidase, lipase, acetylcholinesterase, butyrylcholinesterase, tyrosinase and hyaluronidase. The phenolic profile of the obtained extracts was also investigated by high-performance liquid chromatography with photodiode array detection (HPLC-PAD). The extracts showed inhibitory activity against all enzymes evaluated, with the highest inhibitory activity reported for the enzyme hyaluronidase (28.28 ± 2.43 to 72.19 ± 1.40 μg mL-1). The obtained extracts also demonstrate anti-hemolytic activity (52.22 ± 1.62 to 71.17 ± 1.82%). Among the phenolic compounds identified, protocatechuic, vanillic and β-resorcylic acids were the most abundant (1.13 ± 0.06 to 2.53 ± 0.06, 0.90 ± 0.06 to 2.19 ± 0.06 and 1.03 ± 1.62 to 22.11 ± 1.62 mg L-1, respectively). In the statistical analysis, a significant correlation was found between the flavonoids content and all enzymes inhibitory activities. The present study showed that D. ecastaphyllum leaves extracts may have the potential to be used in the therapeutic treatment of several diseases such as Alzheimer, Parkinson, type 2 diabetes mellitus, hyperglycemia, and pigmentation, as well as those associated with oxidative stress.

Advances and challenges in preclinical evaluation of therapeutic drugs for treating ischemic stroke / 药学学报

Translating of scientific advances into clinical practice is a major challenge in the stroke research field in the past decades. There were many reasons involved:animal models might not accurately capture all aspects of clinical stroke in humans, the blind and randomized design principle was not closely followed, the inclusion and exclusion criteria was not previously established, sample size was inadequate, endpoint was not scientific nor blindly assessed, inadequate reporting of data and statistical flaws. To bridge the gap between experimental and clinical research, international consortia have attempted to establish standardized guidelines for study design and data report, which include optimizing animal models as well as experimental design, using innovative approaches to assess endpoint, making raw data and negative results available, establishing prior registration mechanism, conducting multicenter preclinical randomized controlled trials (pRCTs), systematic reviews and meta-analysis of preclinical studies, evolving the original focus on neuroprotection into a broader consideration of the role of neurovascular unit and ischemic cascade.

Investigación preclínica en las ciencias biomédicas / Pre-clinical biomedical research

Introducción: la perspectiva histórica demuestra lo eficaz y esencial que ha sido la utilización de animales como sujetos de prueba. Se ha logrado salvar vidas y responder a diferentes preguntas biomédicas, a partir de esta práctica. Objetivo: realizar una revisión bibliográfica sobre la investigación preclínica en las ciencias biomédicas. Métodos: se realizó una revisión sobre la investigación preclínica en las ciencias biomédicas en Internet. La búsqueda abarcó artículos publicados fundamentalmente en los últimos 5 años. Se evaluaron revistas internacionales de impacto de la Web of Sciencies relacionadas con el tema (32 revistas) y 2 cubanas. Se consultaron las bases de datos de sistemas referativos, como MEDLINE, PubMed y SciELO con la utilización de descriptores como animal research, preclinical investigation, biomodels, laboratory animals, translational medicine y sus equivalentes en español. Se incluyeron artículos en idioma inglés, portugués y español. Se obtuvieron 136 artículos, se circunscribió el estudio a 53 que enfocaron esta temática de manera más integral. Se revisó 1 libro. Análisis e integración de la información: al analizar el comportamiento de los artículos sobre la temática de estudio respecto a su representatividad en las diferentes revistas científicas donde fueron publicados, 9,4 por ciento de ellos correspondieron a la revista Journal of clinical periodontology e igual porciento a la PloS biology. Los restantes artículos estuvieron distribuidos de manera uniforme entre las otras revistas. La mayoría de las investigaciones sugieren que el empleo de biomodelos constituye una forma eficiente de desarrollar investigaciones, pero que estas deben estar bien diseñadas, pues frecuentemente se introducen sesgos en la validez interna y externa de la investigación, que conllevan a errores en la publicación científica. Conclusiones: el desconocimiento de las características inherentes a los biomodelos, de aspectos propios de la investigación preclínica, los concernientes al diseño metodológico y el mismo desarrollo de la investigación pueden introducir errores en el análisis, y publicación de los resultados; consecuentemente, se afecta la calidad de la investigación, y se contribuye a la frecuente falta de estudios animales confiables(AU)

Introduction: a historical analysis would reveal that the use of animals as test subjects has been both effective and essential. Such a practice has served both to save lives and to answer a variety of biomedical questions. Objective: carry out a bibliographic review about preclinical biomedical research. Methods: abibliographic review was conducted about preclinical biomedical research on the Internet. Most of the papers included in the search have been published in the last five years. An evaluation was performed of international high impact journals from the Web of Sciences dealing with the subject (32 journals), as well as two Cuban journals. Databases from reference systems such as MEDLINE, PubMed and SciELO were consulted with the aid of search terms like animal research, preclinical investigation, biomodels, laboratory animals, translational medicine and their Spanish counterparts. The papers included were in English, Portuguese or Spanish. Of the 136 papers obtained, the reviewers selected the 53 which approached the study subject in a more comprehensive manner. One book was also reviewed. Data analysis and integration: an analysis of the representativeness of papers in the scientific journals where they were published showed that 9.4 percent corresponded to the Journal of Clinical Periodontology, and the same percentage to PloS Biology. The remaining papers were evenly distributed among the other journals. Most studies suggest that biomodels are an effective tool in scientific research, but they should be correctly designed, for it is common to find bias in the internal and external validity of the research, leading to errors in scientific publications. Conclusions: lack of knowledge about characteristics inherent to biomodels, preclinical research, methodological design and the very development of the research may lead to errors in the analysis and publication of results, affecting the quality of the research and contributing to the frequent scarcity of reliable animal studies(AU)

Thrombolysis of plasmin and its derivatives: Research advances / 国际药学研究杂志

All of the thrombolytic agents currently approved for use in humans are plasminogen activators, the application of which is limited by bleeding complications at vascular injury sites and plasminogen content in the thrombus. Plasmin is rapidly neutralized in the circulation by α2-antiplasmin and tolerated without bleeding. With the application of catheter-based delivery, the unique biochemical properties of plasmin make it a safe and effective direct fibrinolytics. Plasmin derivatives, including miniplasmin, {increment}-plasmin and microplsmin, display more thrombolysis efficacy and better hemostatic safety in preclinical study and clinical trials. This review summarizes the current information on plasmin and its derivatives, including the advances on biochemical properties, preclinical and clinical trials.

Thrombolysis of plasmin and its derivatives:research advances / 国际药学研究杂志

All of the thrombolytic agents currently approved for use in humans are plasminogen activators, the application of which is limited by bleeding complications at vascular injury sites and plasminogen content in the thrombus. Plasmin is rapidly neutral-ized in the circulation by α2-antiplasmin and tolerated without bleeding. With the application of catheter-based delivery, the unique bio-chemical properties of plasmin make it a safe and effective direct fibrinolytics. Plasmin derivatives, including miniplasmin,Δ-plasmin and microplsmin, display more thrombolysis efficacy and better hemostatic safety in preclinical study and clinical trials. This review sum-marizes the current information on plasmin and its derivatives, including the advances on biochemical properties, preclinical and clinical trials.