How the gene-editing in medicine and public health practice could stand the test of bioethics / De qué forma la tecnología de edición génica en medicina y salud pública puede ser aceptada al someterse a la reflexión bioética / Como a edição de genes na prática médica e de saúde pública poderia apoiar o teste da bioética

Abstract: 13. In recent years, gene editing is increasingly used as one of the technical means to solve public health problems. The great progress made in the field of life science and gene-editing technology has made it possible for humans to control and alter human physiological characteristics through gene-editing technology and created a broad application prospect for this technology. However, gene-editing technology has faced with many significant ethical risks, and human gene editing experiments have been banned for a long time in the past. Realistic technological breakthroughs and the emergence of real cases force the ethics circle to re-examine this issue. Through the analysis and trade-off of the potential benefits and ethical risks of human gene-editing technology, it can be found that different applications of human gene editing for different purposes are considered to have different acceptability. Among them, human gene editing for medical purposes has no fundamental moral barriers, human gene editing for purposes of enhancement cannot be allowed by ethics and reality in the current social environment, and human gene editing for purposes of transformation fundamentally violates ethical norms. Therefore, gene editing can be allowed if it is only used to solve human medical and public health problems.

Resumen: 17. En años recientes, se usa cada vez más la edición génica como medio técnico para resolver problema de salud pública. El gran progreso realizado en el campo de las ciencias de la vida y la tecnología de edición génica ha hecho posible que el ser humano controle y altere las características fisiológicas humanas, usando esta tecnología y abriéndose una amplia perspectiva de aplicación. Sin embargo, esta tecnología enfrenta problemas éticos significativos, y los experimentos de edición génica en humanos han sido prohibidos por mucho tiempo en el pasado. Los avances tecnológicos realistas y la emergencia de casos reales ejerce presión sobre el círculo de reflexión ética para volver a examinar el tema. Mediante el análisis y balance de los potenciales beneficios y riesgos éticos de la tecnología de edición génica, se puede encontrar que las diferentes aplicaciones de ésta tecnología, para propósitos diferentes, tienen distinta aceptabilidad. Entre ellos, el uso de edición génica para propósitos médicos no tiene barreras morales fundamentales; la edición génica humana para propósitos de mejoramiento no debería permitirse en la realidad social actual, y la edición génica humana para propósitos de transformación viola fundamentalmente las normas éticas. Por lo tanto, la edición génica podría permitirse solamente para resolver problemas médicos y de salud pública en humanos.

Resumo: 21. Em anos recentes, a edição de genes é cada vez mais usada como um recurso técnico para resolver problemas de saúde pública. O grande progresso feito no campo das ciências da vida e da tecnologia de edição de genes tornou possível para os humanos controlarem e alterarem as características fisiológicas humanas através da tecnologia da edição de genes e criou uma ampla perspectiva de aplicação para esta tecnologia. Entretanto, a tecnologia de edição de genes enfrentou muitos riscos éticos significativos e os experimentos de edição de genes humanos foram banidos por muito tempo no passado. Avanços tecnológicos realísticos e a emergência de casos reais forçaram o círculo ético a reexaminar esta questão. Através da análise e do equilíbrio entre os benefícios potenciais e riscos éticos da tecnologia de edição de genes humanos, pode ser encontrado que diferentes aplicações da edição de genes humanos para diferentes propósitos são consideradas ter diferentes aceitações. Dentre elas, a edição de genes humanos com objetivos médicos não tem barreiras morais fundamentais, edição de genes humanos objetivando aprimoramento não pode ser permitida pela ética e realidade do ambiente social atual, e edição de genes humanos objetivando transformação fundamentalmente viola normas éticas. Portanto, edição de genes pode ser permitida somente se usada para resolver problemas médicos humanos e de saúde pública.

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

BACKGROUND: Arsenic trioxide (As2O3), a drug that has been used in China for approximately two thousand years, induces cell death in a variety of cancer cell types, including neuroblastoma (NB). The tyrosine kinase receptor (Trk) family comprises three members, namely TrkA, TrkB and TrkC. Various studies have confirmed that TrkA and TrkC expression is associated with a good prognosis in NB, while TrkB overexpression can lead to tumor cell growth and invasive metastasis. Previous studies have shown that As2O3 can inhibit the growth and proliferation of a human NB cell line and can also affect the N-Myc mRNA expression. It remains unclear whether As2O3 regulates Trks for the purposes of treating NB. METHODS: The aim of the present study was to investigate the effect of As2O3 on Trk expression in NB cell lines and its potential therapeutic efficacy. SK-N-SH cells were grown with increasing doses of As2O3 at different time points. We cultured SK-N-SH cells, which were treated with increasing doses of As2O3 at different time points. Trk expression in the NB samples was quantified by immunohistochemistry, and the cell cycle was analyzed by flow cytometry. TrkA, TrkB and TrkC mRNA expression was evaluated by real-time PCR analysis. RESULTS: Immunohistochemical and real-time PCR analyses indicated that TrkA and TrkC were over-expressed in NB, and specifically during stages 1, 2 and 4S of the disease progression. TrkB expression was increased in stage 3 and 4 NB. As2O3significantly arrested SK-N-SH cells in the G2/M phase. In addition, TrkA, TrkB and TrkC expression levels were significantly upregulated by higher concentrations of As2O3 treatment, notably in the 48-h treatment period. Our findings suggested that to achieve the maximum effect and appropriate regulation of Trk expression in NB stages 1, 2 and 4S, As2O3 treatment should be at relatively higher concentrations for longer delivery times;however, for NB stages 3 and 4, an appropriate concentration and infusion time for As2O3 must be carefully determined. CONCLUSION: The present findings suggested that As2O3 induced Trk expression in SK-N-SH cells to varying degrees and may be a promising adjuvant to current treatments for NB due to its apoptotic effects.