Modelos pré-clínicos de câncer hepático / Preclinical models of liver câncer

ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

RESUMO Contexto: Este manuscrito fornece uma visão geral da carcinogênese hepática em modelos murinos de carcinoma hepatocelular (CHC) e colangiocarcinoma (CCA). Objetivo: Realizar uma revisão de artigos científicos até agosto de 2022 utilizando as bases de dados MEDLINE e EMBASE. Métodos: A busca foi realizada em todas as bases de dados eletrônicas e as palavras-chave usadas foram CHC, CCA, carcinogenesis, modelos animais e fígado. A exclusão dos artigos baseou-se na falta de estreita relação com o assunto. Os modelos de carcinogênese do CHC incluíram: CHC induzido por senescência em animais transgênicos, CHC induzido por dieta, CHC induzido por agentes quimiotóxicos, xenoenxerto, oncogenes e CHC em animais transgênicos inoculados com vírus B e C. Os modelos de CCA incluíram: o uso de dimetilnitrosamina (DMN), dietilnitrosamina (DEN), tioacetamida (TAA) e tetracloreto de carbono (CCl4). Os modelos murinos de CCA induzidos por incluir: células de CCA, manipulação genética, animais nocaute para Smad4, PTEN e p53, xenoenxerto e ligadura do ducto biliar mediano esquerdo. Resultados: Nesta revisão, descrevemos diferentes modelos murinos de carcinogênese que reproduzem os pontos-chave para a gênese do CHC e do CCA, permitindo uma melhor compreensão de suas anormalidades genéticas, fisiopatológicas e ambientais. Conclusão: Cada modelo tem suas vantagens, desvantagens, semelhanças e diferenças com a doença humana correspondente e deve ser escolhido de acordo com a especificidade do estudo. Em última análise, esses modelos também podem ser utilizados para testar novas abordagens terapêuticas anticancerígenas.

Impacto do treinamento físico no perfil inflamatório e redox renal no desenvolvimento de síndrome metabólica / Impact of exercise training on inflammatory and redox renal profiles in metabolic syndrome development

Objetivo: Investigar o efeito do treinamento físico aeróbio (TF) no perfil inflamatório e de estresse oxidativo renal em modelo experimental de desenvolvimento de síndrome metabólica (SM). Métodos: Ratos Wistar e espontaneamente hipertensos (SHR) distribuídos nos grupos: controle (C), hipertenso (H), hipertenso frutose (HF) e hipertenso frutose treinado (HFT). Os grupos HF e HFT foram submetidos à sobrecarga de frutose (10%, 60 dias) desde o desmame. O TF foi realizado em esteira por 60 dias (5dias/semana, 40-60% velocidade máxima do teste de esforço). Resultados: O TF promoveu redução de ânion superóxido, peróxido de hidrogênio e proteínas oxidadas comparado ao grupo HF. Além disso, o grupo HFT apresentou aumento de FRAP e nitritos comparado aos grupos H e HF. No perfil inflamatório, o TF proporcionou aumento de IL-10 e redução da razão TNFα/IL-10. Conclusão: Os resultados demostraram que o treinamento aeróbio atenuou o estresse oxidativo e favoreceu um perfil anti-inflamatório no tecido renal em um modelo de desenvolvimento de SM.

Objective: To investigate the effect of aerobic exercise training (ET) on renal inflammatory and oxidative stress profiles in an experimental model of metabolic syndrome (MS) development. Methods: Wistar and spontaneously hypertensive (SHR) rats were distributed into control (C), hypertensive (H), hypertensive fructose (HF) and trained hypertensive fructose (THF) groups. The HF and THF groups were submitted to fructose overload (10%, 60 days) since weaning. The ET was performed on a treadmill for 60 days (5 days/week, 40-60% maximum speed of the exercise test). Results: The ET promoted reduction in renal superoxide anion, hydrogen peroxide and oxidized proteins compared to the HF group. In addition, the THF group showed an increase in FRAP and in nitrites compared to the H and HF groups. In the inflammatory profile, ET provided an increase in IL-10 and a reduction in TNFα/IL-10 ratio. Conclusion: The results showed that aerobic training attenuated oxidative stress and favored an anti-inflammatory profile in renal tissue in a model of MS development.

Adicción al tabaco y adolescencia: riesgos psicobiológicos / Psychobiological risks of tobacco during adolescence. A narrative review

Resumen La investigación moderna, tanto en humanos como preclínica, que utiliza modelos animales indica que fumar durante la edad adolescente resulta en cambios cerebrales y psicológicos a corto y largo plazo en el fumador, así como en un aumento significativo en los riesgos de desarrollar adicción al tabaco durante la vida. Por lo tanto, en la presente revisión narrativa se describirán y profundizarán los hallazgos investigativos modernos de la psicobiología de la adolescencia y los efectos del tabaco en el desarrollo, con un énfasis particular en la comprensión de los efectos psicológicos y cerebrales del consumo de tabaco durante la adolescencia, tanto a corto como a largo plazo. Se considerarán de manera detallada los avances investigativos sobre la psicobiología de la adolescencia y sus riesgos en las adicciones desde los aspectos: conductual, cognitivo, reactividad al estrés y psicobiología. Sobre esta base, se revisará la investigación sobre la psicobiología de la adolescencia y la evidencia de vulnerabilidad a la adicción durante esta etapa. Al final, se abordarán los efectos del tabaco en el cerebro y conducta durante el desarrollo adolescente y vida posterior, ya que se ha encontrado evidencia relacionada con alteraciones cerebrales crónicas en los sistemas colinérgicos y regiones cerebrales asociadas con la dependencia de la nicotina. Se espera que la revisión y divulgación de esta información en el idioma español sea de valor para la comprensión de los problemas de vulnerabilidad y predisposiciones a la adicción al tabaco en el contexto de Latinoamérica.

Abstract Tobacco use and its harmful health-related problems have become one of the largest modern preventable public health issues. Current research strongly suggests that smoking during adolescence enhances addictive smoking behaviors during life, which can be related to adolescence as a critical ontogenetic period characterized by behaviors that can increase the probability of risk-related behaviors such as sensation and novelty seeking. Adolescent development is also a period of maturation of frontal and subcortical neural systems, brain changes that underlie higher impulsivity tendencies to promote adequate learning and adaptations necessary to succeed the novel challenges of the adult life, but those changes also enhance vulnerabilities to the addictive effects of drugs. Consistent with this, tobacco use affects brain development processes which underlie long-term psychobiological alterations and the enhanced risks for tobacco addiction during adult life. Thus, the present review describes current psychobiological approaches to understand general addiction processes and tobacco addiction, highlighting the behavioral and neural short-term effects of tobacco use during adolescence and its long-term effects during adulthood. Current research has advanced on four aspects for the understanding of both the psychobiology of adolescent development and the effects of drugs of abuse during this time. The first aspect is behavioral, as adolescence is related to important changes on motivational and emotional behaviors such as sensation seeking. Other important behavioral changes are social approach, a higher variety of opportunity for personal choices, and development of personal independence. Research on a second aspect has focused on cognition. A review of research is presented showing enhanced abilities during adolescence development for reading, abstract and logical thinking, and novel problem solving. Stress reactivity is the third aspect of reviewed psychobiological mechanisms. The stress biological system undergoes important changes during adolescence, including changes on stress-related hormones and neural architecture. An important issue is that exposure to early and/or chronic stressful circumstances during adolescence could be related to higher risk to the start and maintenance of addiction states, as suggested by research assessing the disruptive effects of stress on psychobiological homeostatic processes needed to maintain stable biological and emotional regulation. The fourth aspect is psychobiology. In this section research is reviewed related to the development of monoaminergic brain circuits underlying motivation, novelty-seeking, impulsivity, and addiction processes. Using as model the previous review integration, the effects of nicotine are discussed, the essential addictive component of tobacco, on the neurochemical systems underlying tobacco addiction. Following this, important research is introduced that describes psychobiological changes during adolescence and evidence of vulnerability to addiction during this life stage. Then, current research on both short-term and long-term effects of tobacco or nicotine administration during adolescence on the brain, behavior, and cognition is introduced. The current research advances and discussions on the psychobiology of addictions in general, and tobacco addiction in particular, have been possible to a large extent from the use of animal models and preclinical research, since animal models have become crucial to identify learning, motivational, emotional, and cognitive mechanisms that underlie addictive processes, and making possible to perform experimental procedures to discover the functioning and participation of biological components. One example of such components is the cholinergic system, which is activated by nicotine and is part of the neurochemical machinery on different brain areas important for both tobacco addiction and adolescence development such as the dorsal striatum, amygdala, ventral tegmental area, nucleus accumbens, prefrontal cortex, and hippocampus. The present review and research divulgation written in Spanish are expected to clarify modern research on addiction and encourage current scientific education on the vulnerabilities and predispositions for tobacco abuse in Latin-American countries.

Changes of hippocampal gray matter volume and immune related genes in dizocilpine-induced schizophrenia model rats / 中华行为医学与脑科学杂志

Objective:To investigate the changes of hippocampal gray matter volume and expression of candidate immune related genes in a rat model of schizophrenia established by repeated administration of dizocilpine(MK-801).Methods:Thirty SPF grade Sprague-Dawley male rats at postnatal day 28 were randomly divided into MK-801 medium-dose (0.25 mg/kg) group, MK-801 high-dose(0.50 mg/kg) group and normal saline (5 mL/kg) group according to random number table method, with 10 in each group.Rats were given continuous intraperitoneal administration according to grouping once a day for 14 days.Open field test, novel object recognition test and Y-maze test were used at postnatal day 60 to detect spontaneous activity, exploration ability, anxiety level, object recognition memory ability and spatial working memory of rats, respectively.At postnatal day 67, structural magnetic resonance imaging was used to detect the changes of hippocampal gray matter volume in rat.And at postnatal day 70, qRT-PCR was used to detect the expression of candidate immune-related genes in rat hippocampus.SPSS 25.0 was used for statistical analysis, one-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparisons.Results:(1)The behavioral results showed that there were significant differences in the total movement distance, central area activity time, novel object recognition index, and spontaneous correct alternation rate among the three groups ( F=11.15, 10.11, 13.62, 11.99, all P<0.05). The total movement distances in MK-801 medium-dose group and MK-801 high-dose group ((21.44±2.17) m, (22.87±1.96)m) were higher than that in the normal saline group ((18.70±1.88) m) (both P<0.05). The activity time of the central area in the MK-801 medium-dose group and MK-801 high-dose group((3.24±1.58) s, (2.50±1.32) s) were lower than that of the normal saline group ((6.05±2.48)s) (both P<0.01). Novel object recognition indexes in the MK-801 medium-dose group and MK-801 high-dose group((56.10±3.99)%, (54.00±6.41)%) were both lower than that in the normal saline group ((65.90±5.65)%)(both P<0.01), and the rates of spontaneous correct alternation ((54.60±7.03)%, (51.60±8.84)%) in the two groups were lower than that of the normal saline group ((68.40±8.57)%) (both P<0.01). (2) The results of structural magnetic resonance imaging showed that there were significant differences in the volume of hippocampal gray matter among the three groups ( F=9.24, P<0.001). The volumes of hippocampal gray matter in MK-801 medium-dose group and MK-801 high-dose group were lower than that in normal saline group(both P<0.001). (3)By constructing protein-protein interaction network, four candidate immune related genes were screened out: neuropeptide Y (NPY), somatostatin (SST), cholecystokinin (CCK) and tachykinin 1 (TAC1). The results showed that the mRNA expression levels of NPY, SST and CCK in the hippocampus of the three groups were significantly different ( F=11.41, 10.43, 5.85, all P<0.05), but there was no statistical difference in the TAC1 mRNA expression level ( F=0.08, P>0.05). The mRNA levels of NPY, SST and CCK in the hippocampus of rats in the MK-801 high-dose group were lower than those in the normal saline group (all P<0.05). Conclusion:Both medium dose and high dose MK-801 administration can reduce the volume of hippocampal gray matter in schizophrenia model rats, but they have different effects on the expression of hippocampal immune related genes, of which high dose administration has a greater effect.

Evaluation of Animal Models of Acute Lung Injury Caused by Non-physical Factors Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo study the characteristics of animal models of acute lung injury caused by non-physical factors， so as to provide a reference for the standardization of the preparation of such animal models and lay a foundation for the research on the pathogenesis and the diagnosis and treatment of acute lung injury. MethodThe articles about the animal experiments of acute lung injury published in the last decade were retrieved from China National Knowledge Infrastructure （CNKI）， Wanfang， SinoMed， VIP， and PubMed with the theme terms of "acute lung injury" and "animal model". The animal species， drugs used in modeling， modeling period， methods used in molding， model standards， and model evaluation indicators were summarized， and Excel was used for the frequency analysis. ResultA total of 338 articles were included in this study. The results of the frequency analysis showed that SD rats/C57BL/6 mice were mainly used to establish the animal models of acute lung injury. Male mice were mostly used for modeling， and the commonly used modeling agent was lipopolysaccharides （LPS）. In most cases， the modeling lasted for 6 h after drug administration. Hematoxylin-eosin staining was mainly used for the observation of histological changes in the lungs， which were taken as the criteria for modeling. The established models were mainly evaluated based on lung dry/wet weight ratio， lung index， morphological changes in the lung tissue， myeloperoxidase （MPO）， superoxide dismutase （SOD）， and levels of inflammatory cytokines in the serum and bronchoalveolar lavage fluid （BALF）. ConclusionThe models of acute lung injury were mostly prepared by intraperitoneal injection of LPS （5 mg·kg-1） in SD rats and tracheal instillation of LPS （5 mg·kg-1） in C57BL/6 mice， which were praised for the simple operation， high success rate， and consistent with the pathogenesis of acute lung injury. This study provides a reference for the basic research on acute lung injury by animal experiments.

Common problems and considerations in challenge tests of different animal models of SARS-CoV-2 vaccine / 中国生物制品学杂志

@#Animal challenge test is an effective means to study the efficacy of severe acute respiratory symptom coronavirus 2(SARS-CoV-2)vaccine. The appropriate animal models and reasonable experimental design play an important role in obtaining efficacy and safety information,as well as supporting clinical trials. At present,common non-clinical animal models include transgenic mice,non-human primates,hamsters,ferrets and so on. This paper reviews the common animal models used in non-clinical trials and the problems encountered in their application.

Construction and management model practice of a patient-derived xenograft model platform / 中华医学科研管理杂志

Objective:In the era of precision medicine, there is an urgent need for a preclinical evaluation method with a high cost-benefit ratio to improve the effectiveness and value of clinical trials.Methods:Taking clinical needs and scientific research purposes as the starting point, the platform focused on four aspects of project management, information retrieval, quality control, and practical application, and introduced in detail the management practice of building a patient-derived xenograft model platform system.Results:With the support of the institutional system, quality control system, and information system, the patient-derived xenograft model platform was formed with standardization as the core. With the assistance of this platform and scientific research management, as of December 2021, there are 48 animal models of patient-derived xenograft in the database. In total of 6 SCI scientific and technological articles were published using these animal models, with a total impact factor of 36.77 (the highest single article was 7.333). In total of 6 direct industrial projects, 6 clinical trial-related projects, and 4 NSFC projects were approved with a total research fund of 1.5 million yuan.Conclusions:Continuous construction and improvement of the existing platform will help promote the development of basic research translation and clinical research in the field of oncology, and accelerate the development of new oncological diagnosis and treatment models, thereby benefiting more patients.

Establishment of animal models for depression in the elderly and progress on their application / 中华老年医学杂志

Geriatric depression in the elderly is becoming one of the most common psychiatric disorders affecting older people's mental and physical health.However, there is currently no systematic review on animal models for geriatric depression.Therefore, this paper analyzes and summarizes the animal models commonly used in geriatric depression studies and the application of antidepressants in geriatric depression models based on relevant national and international literature of recent years, aiming to provide insights on research approaches and considerations on study methods for geriatric depression.

"Disease-syndrome-therapy" Spontaneous Abortion Models and Application Trends of Single-cell Multimodal Omics： A Review / 中国实验方剂学杂志

The incidence of spontaneous abortion （SAB） has been increasing year by year， and its etiology is complex， with limited treatment options， which poses a serious threat to social stability. The "disease-syndrome-therapy" research model can significantly improve the clinical efficacy of traditional Chinese medicine （TCM） for preventing miscarriage， but there has always been a lack of key and recognized diagnostic and treatment evaluation markers， which need to be further explored to establish a scientific and unified evaluation standard system. It is proposed to collect existing "disease-syndrome-therapy" SAB animal models， transplant and improve the model evaluation indicators， evaluate the degree of match between SAB animal models and the clinical characteristics of TCM and Western medicine diseases and syndromes， and compare the advantages and disadvantages of different SAB animal models in terms of construction methods， target selection， and evaluation indicators. In addition， the frontiers of TCM experimental research will be explored. In view of the current status and related bottlenecks of molecular biomarkers research on SAB TCM animal models， a single-cell multimodal omics research strategy will be proposed to break through the related evaluation defects of the "disease-syndrome-therapy" SAB and analyze the differences in various cell types， cell subpopulations， spatiotemporal trajectories， and gene expression in the mother-fetal interface tissue at the single-cell level. This will provide accurate guidance and model animal platform support for the in-depth study of disease-syndrome models， Zang-fu biology， and novel targeted drugs. It will also provide a basis for establishing a stable and repeatable "disease-syndrome-therapy" SAB animal model and evaluation indicator system， which is beneficial for the long-term development of TCM reproductive animal model research.

Research progress on genetic model of mouse with glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

Glaucoma, currently the world's first irreversible blindness, is a complex multifactorial disease with a genetic predisposition, and pathologically elevated intraocular pressure is its risk factor. The pathogenesis of glaucoma is not fully understood, and most existing studies are based on animal models, with mice as the main research object, and the pathological damage process of glaucoma is reconstructed through experimental induction means or transgenic manipulation to further investigate the relevant pathogenesis and pathological changes. The technique of experimentally induced construction of glaucoma mouse models has been studied by many scholars and is gradually becoming mature. And as research in molecular biology and genetics has advanced, more and more studies have focused on the disease genes associated with glaucoma, and transgenic mouse models have become a hot topic in recent years. In contrast to experimental manipulation to control a single factor, gene editing is better able to simulate the complex process of disease pathogenesis. This paper focuses on providing a more complete direction and strategy for model selection in the future research by describing the progress of research on relevant transgenic mouse model of glaucoma.

Establishment and Evaluation of Animal Models of Chronic Fatigue Syndrome / 中国实验方剂学杂志

Chronic fatigue syndrome （CFS） is a heterogeneous disease with dysfunction in multiple systems and multiple organs. Its etiology and pathogenesis have not been fully clarified， and its treatment also lacks specificity. The key to studying CFS is developing animal models that reflect the underlying mechanisms and etiology of CFS. The existing CFS modeling methods are complicated and not unified. By sorting out relevant literature，the present study evaluated the modeling methods，modeling standards，mechanisms， and clinical coincidence of the immune model，the stress model， and the disease-syndrome combination model in traditional Chinese medicine （TCM）. The immune model is mainly constructed from the perspective of pathophysiology， with easy operation and wide investigation， which can simulate the pathological characteristics of CFS to ensure pathogenesis research，but the experimental repeatability is general. Stress modeling is a common method for a variety of neuropsychiatric diseases，including CFS. Many different stressors can be employed to investigate the etiology of CFS， but their effects are unpredictable. Compared with the two western medicine models mentioned above，the TCM disease-syndrome combination model integrates modern medicine with TCM theory，with high clinical coincidence and great practical value. However，the TCM disease-syndrome combination model of CFS is still in the exploratory stage with a few types of models，which needs to be further improved， aiming to establish scientific，reasonable，simple， and efficient animal models to provide support for exploring the etiology，pathogenesis， and new treatment ideas of CFS.

Comparison of three methods for establishing rat peri-implantitis model / 北京大学学报(医学版)

OBJECTIVE@#To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods.@*METHODS@#Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1β (IL-1β). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death.@*RESULTS@#After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1β in the test groups were higher than those in the control group (P < 0.05).@*CONCLUSION@#Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.

Advances in animal models of chronic heart failure and its applications in traditional Chinese medicine / 中国中药杂志

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.

Research progress on animal models of contrast-induced acute kidney injury / 中南大学学报(医学版)

Contrast-induced acute kidney injury (CI-AKI) refers to acute kidney injury that occurs after intravascular contrast media is applied. It is the third most common cause for acute renal failure in hospitalized patients and can cause severe renal impairment and adverse cardiovascular outcomes. In severe cases, it can even lead to the death of the patient. Due to its complicated pathogenesis, the pathogenesis of CI-AKI has not yet been elucidated. Therefore, it is of great significance to further study the pathogenesis for the prevention of CI-AKI. Moreover, a good animal model of CI-AKI is an important tool for in-depth research on the pathogenesis of acute kidney injury induced by contrast agents.

Feasible low bone density condition for assessing bioactivity in ex-in vivo and in vivo studies

Abstract Objective To choose a critical animal model for assessments of bone repair with implant installation by comparing senile rats (SENIL) to young ovariectomized rats (OXV). Methodology For the ex-in vivo study, the femurs were precursors for bone marrow mesenchymal stem cells. Cellular responses were performed, including cell viability, gene expression of osteoblastic markers, bone sialoprotein immunolocalization, alkaline phosphatase activity, and mineralized matrix formation. For the in vivo study, the animals received implants in the region of the bilateral tibial metaphysis for histometric, microtomography, reverse torque, and confocal microscopy. Results Cell viability showed that the SENIL group had lower growth than OVX. Gene expression showed more critical responses for the SENIL group (p<0.05). The alkaline phosphatase activity obtained a lower expression in the SENIL group, as for the mineralization nodules (p<0.05). The in vivo histological parameters and biomechanical analysis showed lower data for the SENIL group. The confocal microscopy indicated the presence of a fragile bone in the SENIL group. The microtomography was similar between the groups. The histometry of the SENIL group showed the lowest values (p<0.05). Conclusion In experimental studies with assessments of bone repair using implant installation, the senile model promotes the most critical bone condition, allowing a better investigation of the properties of biomaterials and topographic changes.

Therapeutic potential of Punica granatum in wound healing: An overview

SUMMARY Objective: This review aim to report the results of the most recent research and applications of different extracts of P. granatum in the in vivo wound healing process. Methods: For the survey of articles in literature, a search was conducted in the PubMed, Scopus, Science Direct and Science Citation Index Expanded (Web of Science) databases. Results: Punica granatum is a plant native to Iran and adjacent regions widely used worldwide as a food and medicinal source. Its healing property is closely linked to the presence of phenolic compounds, tannins and flavonoids, and its concentration in treatment formulations seems to be determinant for the acceleration of tissue repair, although few data on the standardization and stability of these formulations are available. Studies on experimental models were able to demonstrate the repair potential of P. granatum; however, human studies are still scarce. Conclusions: This contribution summarizes the use of P. granatum extracts in healing different types of lesions, emphasizing its effects on inflammatory, prolif-erative, and remodeling phases.

Objetivo: Relatar los resultados de investigaciones y aplicaciones más recientes de diferentes extractos de P. granatum en el proceso de cicatrización de heridas in vivo. Métodos: Para encuesta de artículos en la literatura, se realizó búsqueda en las bases de datos PubMed, Scopus, Science Direct y Science Citation Index Expanded (Web of Science). Resultados: Punica granatum es una planta originaria de Irán y regiones adyacentes, ampliamente utilizada en todo el mundo como fuente alimenticia y medicinal. Su propiedad cicatrizante está íntimamente ligada a la presencia de compuestos fenólicos, taninos y flavonoides, y su concentración en las formulaciones de tratamiento parece ser determinante para aceleración de la reparación tisular, aunque se dispone de pocos datos sobre estandarización y estabilidad de estas formulaciones. Estudios sobre modelos experimentales pudieron demostrar el potencial de reparación de P. granatum; sin embargo, los estudios en humanos aún son escasos. Conclusiones: Este aporte resume el uso de extractos de P. granatum en la curación de diferentes tipos de lesiones, enfatizándose sus efectos en las fases inflamatoria, proliferativa y remodeladora.

Objetivo: Relatar os resultados de pesquisas mais recentes e aplicações de diferentes extratos de P. granatum no processo de cicatrização in vivo. Métodos: Para levantamento de artigos na literatura, realizou-se busca nas bases de dados PubMed, Scopus, Science Direct e Science Citation Index Expanded (Web of Science). Resultados: Punica granatum é uma planta nativa do Irã e das regiões adjacentes, amplamente utilizada em todo o mundo como alimento e fonte medicinal. A propriedade cicatrizante está intimamente ligada à presença de compostos fenólicos, taninos e flavo-noides, cuja concentração nas formulações de tratamento parece ser determinante para aceleração do reparo tecidual, embora poucos dados sobre a padronização e estabilidade dessas formulações estejam disponíveis. Estudos em modelos experimentais foram capazes de demonstrar o potencial de reparo de P. granatum. No entanto, estudos em humanos ainda são escassos. Conclusões: Esta contribuição resume o uso de extratos de P. granatum na cicatrização de diferentes tipos de lesões, enfatizando os efeitos nas fases inflamatória, proliferativa e remodelação.

Experimental carcinogenesis with 7, 12-dimethylbenz(a)anthrazene (DMBA) and its inhibition with isothi-ocyanates / Carcinogénesis experimental con 7, 12-dimetilbenzantraceno (DMBA) y su inhibición con isitiocianatos

Introduction: DMBA is a chemical carcinogen that induces carcinomas within a few weeks of its application. We developed an experimental model of carcinogenesis induced by DMBA dissolved in 0,5% paraffin oil (DMBA-PO), verifying the inhibitory effect of the carcinogenicity of phenyl isothiocyanate (PhITC), phenethyl (PhnITC) and benzyl isothiocyanate (BITC). Material and Methods: For this, 88 hamsters were distributed into three groups: one exposed to DMBA-PO (Group 1, n=12), three subgroups (n=12) exposed to PhITC, PhnITC, BITC and DMBA-PO (Group 2, n=36) and four control subgroups (n=10) that were not exposed to the carcinogen in which PO (paraffin oil) and isothiocyanates were applied (Group 3, n=40). Results: The experiment had a duration of 20 weeks, at the end of which the inhibitory effect was established by comparing the lesions developed in the groups that received isothiocyanates with the group that was only treated with DMBA-PO. The carcinogenic effect of DMBA-PO is 100% (35 carcinomas) and the inhibitory effect was 0, whereas in the presence of isothiocyanates the carcinogenic effect decreases, with an inhibitory effect of 86% for BITC (5 carcinomas) and 74% for PhITC (9 carcinomas). Conclusion: The inhibitory effect for PhnITC is 80% in relation to invasive OSCC (1 carcinoma).

Introducción: El DMBA es un carcinógeno químico que induce carcinomas a las pocas semanas de su aplicación. Desarrollamos un modelo experimental de carcinogénesis inducida por DMBA disuelto en aceite de parafina al 0,5% (DMBA-Ap) comprobando el efecto inhibidor de la carcinogénesis de los isotiocianatos fenil (PhITC), fenetil (PhnITC) y bencil isotiocianato (BITC). Material y Métodos: Para ello, se distribuyeron 88 hámsteres en 3 grupos: uno expuesto al DMBA-Ap (Grupo 1, n=12), tres subgrupos (n=12) expuestos a PhITC, PhnITC, BITC y DMBA-Ap (Grupo 2, n=36) y cuatro subgrupos controles (n=10), no expuestos al carcinógeno en el que se aplicaron Ap e isotiocianatos (Grupo 3, n=40). Resultados:El experimento tuvo una duración de 20 semanas, al final de la cual se establece de forma comparativa el efecto inhibidor comparando las lesiones desarrolladas en los grupos que recibieron isotiocianatos con respecto al grupo tratado sólo con DMBA-Ap. El efecto carcinógeno del DMBA-Ap es del 100% (35 carcinomas) y el efecto inhibidor 0, mientras que en presencia de isotiocianatos el efecto carcinógeno disminuye, con un efecto inhibidor del 86% para BITC (5 carcinomas) y del 74% para el PhITC (9 carcinomas). Conclusión:El efecto inhibidor del PhnITC es del 80% en relación con el COCE invasivo (1 carcinoma).

A Review on Medicinal Plants with Potential Nootropic Activity along with Animal Models Needed for their Screening

Dementia is a brain disorder marked by cognitive dys functioning which causes loss of learning , thinking and memory .Various drugs that possess nootropic activity are used for treatment of dementia but emerges side effects. To overcome these side effects plants with medicinal importance came into existence. India has wide variety of medicinal plants (Centella asiatica, Clitoria ternatea ,Ginkgo biloba, Curcuma longa etc) that has been claimed for nootropic activity with limited side effects. Nootropic activity of medicinal plants can be screened with various animals models that has been able to identify chemicals with potential therapeutic efficacy. The current review article rehabilitates knowledge of medicinal plants with nootropic action, as well as the animal models needed to screen them.

Perspectiva bioética para México, España y Estados Unidos en los modelos in vivo de inducción de daño al ADN

En la actualidad, la investigación biomédica se ha centrado en el estudio de enfermedades como el cáncer, que causan un elevado índice de mortalidad. Existen diferentes modelos animales, empleados para generar diversos tipos de carcinogénesis; el daño directo al ADN es uno de los mecanismos más utilizados. Sin embargo, en la normatividad nacional e internacional vigente, no se señalan los aspectos bioéticos que se deben seguir para desarrollar un modelo experimental de daño al ADN. Además, no se realiza una correcta semejanza de la enfermedad. Debido a lo anterior, esta revisión analiza los avances en cuanto a normatividad que se han generado en diferentes países, comparando los estudios encontrados en Estados Unidos, México y España. La perspectiva a futuro es poder contar con guías de experimentación actualizadas, que permitan pautar las normas necesarias para el adecuado desarrollo de los modelos de investigación animal de daño al ADN y que cumplan con la regla de las 3R en la experimentación animal. Esta iniciativa se debe de realizar en conjunto entre la Organización Mundial de la Salud y los organismos especializados en manejo y cuidado de animales de laboratorio en los ámbitos nacional e internacional.

Currently, biomedical research has focused on the study of diseases such as cancer that causes a high mortality rate. Different animal models are used to generate different types of carcinogenesis; direct DNA damage is one of the most used mechanisms. However, current national and international regulations do not indicate the bioethical aspects that must be followed to develop an experimental model of DNA damage. In addition, they do not perform a correct resemblance of the disease. Due to the above, this review analyzes the advances in regulations generated in different countries, comparing the studies found in the United States, Mexico, and Spain. The future perspective is to be able to count on updated experimentation guidelines, which allow the establishment of the necessary norms for the adequate development of animal research models of DNA damage that comply with the 3R rule in animal experimentation. This initiative should be carried out jointly by the World Health Organization and organizations specialized in managing and caring laboratory animals at the national and international levels.

Na atualidade, a pesquisa biomédica vem se focando no estudo de doenças que causam um elevado índice de mortalidade, como o câncer. Existem diferentes modelos animais utilizados para gerar diversos tipos de carcinogêneses; o dano direto ao DNA é um dos mecanismos mais utilizados. Contudo, na legislação nacional e internacional vigente, não são sinalizados os aspectos bioéticos que devem ser seguidos para desenvolver um modelo experimental de dano ao DNA, além de não ser realizada uma correta semelhança da doença. Devido a isso, esta revisão analisa o avanço quanto à legislação que vem sendo gerada em diferentes países, comparando os estudos encontrados nos Estados Unidos, no México e na Espanha. A perspectiva para o futuro é poder contar com atualizadas, que permitam estabelecer as normas necessárias para desenvolver os modelos de pesquisa animal de dano ao DNA e que cumpram com a regra das 3R na experimentação animal. Essa iniciativa se deve realizar em conjunto entre a Organização Mundial da Saúde e as organizações especializadas na gestão e cuidado de animais de laboratório nos contextos nacional e internacional.

Incisional hernia repair in rats: description of the sublay technique under videomagnification system

Purpose: To describe the technique of sublay correction of incisional hernia in Wistar rats under videomagnification system. Methods: Five male rats of the species Rattus norvegicus, of the Wistar lineage, with body weight between 250­350 g and 60 days old were used. Incisional hernia was inducted in all animals. After that, the incisional hernia was immediately corrected by the sublay method. Results: There were no cases of recurrence of the incisional hernia after placement of the polypropylene mesh using the sublay technique. No postoperative complications were observed. Conclusions: The technique is suitable for execution in Wistar rats.