ABSTRACT
ABSTRACT The delivery of nucleic acids to cells is considered a crucial step for the success of genetic modifications aimed at therapeutic purposes or production of genetically modified animals. In this context, nanotechnology is one of the most promising fields of science, with the potential to solve several existing problems. Nanostructures have desirable characteristics to be used as carriers, such as nanometric size, large surface area, cell internalization capacity, prolonged and controlled release, among others. Genetically modified animals can contribute to the production of biopharmaceuticals, through the expression of high-associated-value molecules. The production of these animals, also known as biofactories, further enhances Brazilian agribusiness, since it allows adding value to the final product, and favors the integration between the agricultural market and the pharmaceutical sector. However, there is a growing concern about the safety and possible harmful effects of nanostructures, since data on the safe use of these materials are still insufficient. The objective of this review was to address aspects of the use of nanostructures, mainly carbon nanotubes as nucleic acid carriers, aiming at the production of genetically modified animals, with the certainty that progress in this field of knowledge depends on more information on the mechanisms of interaction between nanostructures, cells and embryos, as well as on its toxicity.
Subject(s)
Animals , Nucleic Acids , Nanotubes, Carbon , Nanostructures/toxicity , Nanostructures/chemistry , Drug Delivery Systems , NanotechnologyABSTRACT
<p><b>OBJECTIVE</b>To explore repairing results of VEGF165 gene modified adipose-derived stem cells for diabetic rats with bone defect.</p><p><b>METHODS</b>Seventy-eight male Wistar rats weighted 180 to 220 g were selected, 72 rats were established diabetic animal models by streptozotocin inducement method, blood glucose level was more than 16.7 mmol/L. Experimental animals were randomly divided into 5 groups, 6 rats in normal group and each 18 rats in other groups. VEGF165 gene modified adipose-derived stem cells were implanted into normal group with bone defect; single diabetic rats with bone defect were named as diabetic group;vascular endothelial growth factor implanted into single diabetic rats with bone defect named as growth factor group; adipose-derived stem cells implanted into diabetic rats with bone defect names as stem cell group; VEGF165 gene modified adipose-derived stem cells implanted diabetic rats with bone defect named as experimental group. After combination of VEGF165-ADSCs (5×106) cells combined with gel sponge, implanted into diabetic rats with bone defect. On the forth week, general form of defect repairing tissue were observed by optical microscopy;local density of micro-vessel were detected by immunohistochemistry method; content of Ca, P and ALP of repairing callus were detected by IRIS Intrepid XSP inductively coupled plasma emission spectrometer. Efficacy of the VEGF165-ADSCs repairing function was evaluated by SPSS statistic software.</p><p><b>RESULTS</b>Fluorescent staining results showed that expression of VEGF165 located on cytoplasm of ADSCs, expression percentage was more than 87%; general histology results showed that callus formation and quality was near to normal group, repairing results in diabetes group, growth factor group and stem cell group were poor. On the Forth week after implantation, content of Ca, P and ALP of repairing callus in experimental group were higher than those in growth group and stem cell group, and without significant differences compared with normal group; blood vessel density in experimental group was lower than normal group, but higher than other groups.</p><p><b>CONCLUSIONS</b>VEGF165 gene modified adipose-derived stem cells for repairing diabetic rats with bone defect has advantages of osteogenesis and angiogenesis, and should be one of the effective method for repairing diabetic rats with bone defect.</p>
ABSTRACT
En la investigación con animales existen cuestionamientos éticos tanto en su uso como modelos de enfermedades humanas y el ser requisito previo para ensayos en humanos, como en la introducción de modificaciones genéticas. Algunos de estos cuestionamientos se refieren a que no representan completamente la condición humana como modelo; que realizar pruebas de toxicidad causan grave daño a los animales; que se altera su naturaleza mediante modificaciones genéticas y el riesgo de introducir organismos genéticamente modificados. El uso de animales en investigación para beneficio humano impone la responsabilidad moral de respetarlo, no haciéndoles sufrir innecesariamente, puesto que se está trabajando con seres vivos con capacidad de sentir.
Research with animals presents ethical questions both for being used as models of human diseases and for being a prerequisite for trials in humans, as in the introduction of genetic modifications. Some of these questions refer to the fact that, as models, they do not fully represent the human condition; that conducting toxicity tests causes great harm to animals; that their nature is altered by genetic modifications and that introducing genetically modified organisms is a risk. The use of animals in research for the benefit of humans imposes the moral responsibility to respect them, not making them suffer unnecessarily, since they are living beings capable of feeling.
Subject(s)
Animals , Animal Experimentation , Genetic Research , Animal Welfare , Animals, Genetically Modified , Bioethical IssuesABSTRACT
Formas químicas de controle de mosquitos vetores são ineficazes, levando ao desenvolvimento de novas estratégias. Assim, foi realizada revisão das estratégias de controle genético de populações de mosquitos vetores baseada na técnica do inseto estéril. Uma delas consiste na liberação de machos esterilizados por radiação, a outra, na integração de um gene letal dominante associado a um promotor específico de fêmeas imaturas. Entre as vantagens sobre outras técnicas biológicas e químicas de controle de vetores estão: alta especificidade, não prejudicial ao meio ambiente, baixo custo de produção e alta eficácia. O uso desta técnica de modificação genética pode vir a ser uma importante ferramenta do manejo integrado de vetores.
The ineffectiveness of current strategies for chemical control of mosquito vectors raises the need for developing novel approaches. Thus, we carried out a literature review of strategies for genetic control of mosquito populations based on the sterile insect technique. One of these strategies consists of releasing radiation-sterilized males into the population; another, of integrating a dominant lethal gene under the control of a specific promoter into immature females. Advantages of these approaches over other biological and chemical control strategies include: highly species-specific, environmentally safety, low production cost, and high efficacy. The use of this genetic modification technique will constitute an important tool for integrated vector management.
Subject(s)
Animals , Male , Female , Animals, Genetically Modified , Culicidae/genetics , Insect Vectors/genetics , Mosquito Control/methods , Sensitivity and SpecificityABSTRACT
Hypertrophic cardiomyopathy is an autosomal-dominant disease.Disease-causing mutations have been found in genes encoding structural components of the thick and thin filament systems of cardiac myocyte;it has therefore been named as a disease of sarcomere.Many approaches have been used to characterize the pathogenesis of the desease.Transgenic animal models have been created to gain further insight into the pathogenesis of this disease.Most of these models has been made in mice;however,recently a transgenic rabbit model has been created.In addition,there are several natural-occurring forms of HCM in animals.The discovery of responsible genes and the elucidation of the molecular mechanisms of pathogenesis through the use of animal models promise improved and early diagnosis and the potential for mechanism-based therapeutics.