AVANÇOS EM BIOTECNOLOGIA PARA A REGENERAÇÃO CELULAR E TECIDUAL: DESAFIOS E PERSPECTIVAS NO TRATAMENTO DE DOENÇAS HUMANAS

Biotechnology constitutes a realm of inquiry that extends its benefits across diverse domains of knowledge, ranging from agricultural sciences to clinical applications. This field leverages technology to address challenges frequently entailing living organisms. Of current significance is the endeavor to elucidate the process of animal regeneration, particularly within the human species, given its burgeoning potential as an ally in the treatment and cure of various maladies. Recognizing the societal importance of this subject, the present article seeks to expound upon contemporary biotechnological advancements facilitating the exploration of cellular and tissue regeneration for the treatment of human diseases. To this end, a comprehensive review of articles delineating the current landscape was conducted, involving a comparative analysis of regenerative activity across species, with a specific focus on humans. Evidentially, the use of biomaterials in tissue regeneration assumes paramount importance, albeit not without the formidable challenge posed by the inflammatory process. Stem cells, conversely, present themselves as promising entities in the realm of regeneration. However, their interaction within the host organism necessitates further scrutiny to attain a more nuanced understanding. Despite strides made in the field of regenerative medicine, the lack of comprehensive comprehension regarding the properties of biomaterials and their responses within the human body constrains their clinical applicability. Nevertheless, an auspicious future is envisioned, marked by advancements in biomaterials and a heightened understanding of interactions within the human body, thereby fostering the development of more efficacious treatments for a myriad of diseases.La biotecnología es un campo de investigación que beneficia diversas áreas del conocimiento,desde las ciencias agrarias hasta las aplicaciones clínicas, utilizando tecnologías para abordarproblemas que a menudo involucran organismos vivos. Un gran interés en este campo en laactualidad es dilucidar el proceso de regeneración animal, especialmente en los humanos, ya quese ha convertido en un aliado potencial en la cura y tratamiento de diversas enfermedades. Dadala importancia de este tema para la sociedad, este artículo tiene como objetivo discutir los avancesbiotecnológicos actuales que ayudan a aprovechar el potencial de la regeneración celular y tisularen el tratamiento de enfermedades humanas. Con este fin, se realizó una compilación de artículosque describen el escenario actual, analizando comparativamente la actividad regenerativa entreespecies y humanos. A partir de la exposición, fue posible constatar que el uso de biomateriales enla regeneración tisular es crucial, pero el proceso inflamatorio representa un gran desafío. Lascélulas madre, por otro lado, parecen ser prometedoras en el campo de la regeneración; sinembargo, su interacción en el organismo huésped necesita un estudio más profundo para unamejor comprensión. A pesar del progreso en la medicina regenerativa, la falta de comprensiónsobre las propiedades de los biomateriales y sus respuestas en el cuerpo limitan su aplicaciónclínica. No obstante, se espera un futuro prometedor con avances en biomateriales y unacomprensión más profunda de las interacciones en el cuerpo humano, promoviendo tratamientosmás efectivos para diversas enfermedades.Biotechnology constitutes a realm of inquiry that extends its benefits across diverse domains of knowledge, ranging from agricultural sciences to clinical applications. This field leverages technology to address challenges frequently entailing living organisms. Of current significance is the endeavor to elucidate the process of animal regeneration, particularly within the human species, given its burgeoning potential as an ally in the treatment and cure of various maladies. Recognizing the societal importance of this subject, the present article seeks to expound upon contemporary biotechnological advancements facilitating the exploration of cellular and tissue regeneration for the treatment of human diseases. To this end, a comprehensive review of articles delineating the current landscape was conducted, involving a comparative analysis of regenerative activity across species, with a specific focus on humans. Evidentially, the use of biomaterials in tissue regeneration assumes paramount importance, albeit not without the formidable challenge posed by the inflammatory process. Stem cells, conversely, present themselves as promising entities in the realm of regeneration. However, their interaction within the host organism necessitates further scrutiny to attain a more nuanced understanding. Despite strides made in the field of regenerative medicine, the lack of comprehensive comprehension regarding the properties of biomaterials and their responses within the human body constrains their clinical applicability. Nevertheless, an auspicious future is envisioned, marked by advancements in biomaterials and a heightened understanding of interactions within the human body, thereby fostering the development of more efficacious treatments for a myriad of diseases.A biotecnologia é um campo de pesquisa que beneficia várias áreas de conhecimento, desde as ciências agrárias até ao uso clínico, recorrendo a tecnologias para resolver problemas que, muitas vezes, envolvem organismos vivos. Um grande interesse deste ramo, atualmente, é esclarecer o processo de regeneração animal, especialmente na espécie humana, uma vez que se tornou um aliado potencial na cura e no tratamento de várias doenças. Dada a importância deste assunto para a sociedade, o presente artigo procura abordar os atuais avanços biotecnológicos que ajudam na busca por utilizar a potencialidade da regeneração celular e tecidual no tratamento de doenças humanas. Para esse efeito, foi realizada uma revisão de artigos que descrevessem o cenário atual, analisando comparativamente a atividade regenerativa entre espécies e seres humanos. A partir do exposto, foi possível verificar que a utilização de biomateriais na regeneração tecidual é crucial, porém o processo inflamatório é um grande desafio. Já as células-tronco mostram ser uma promessa na área de regeneração, no entanto, a sua interação no organismo hospedeiro precisa ser mais bem estudada para se obter um melhor entendimento. Apesar do progresso na medicina regenerativa, a falta de compreensão sobre as propriedades dos biomateriais e suas respostas no corpo limitam a sua aplicação clínica. Ainda assim, espera-se um futuro promissor com avanços nos biomateriais e uma compreensão mais profunda das interações no corpo humano, promovendo tratamentos mais eficazes para diversas doenças

ANÁLISE DE GENES DIFERENCIALMENTE EXPRESSOS EM AMOSTRAS DE CÂNCER DE MAMA DO SEQUENCE READ ARCHIVE (SRA)

Breast cancer (BC) is a highly prevalent disease in women with millions of new cases each year. Among the technological advances, RNA-seq technology stands out, which has allowed us to better understand gene expression, making it possible to unveil protein interactions between early and recurrent (post-mastectomy) breast tumors. New tools based on bioinformatics have emerged to follow the advancement of sequencing, with the main examples being the online analysis platforms Galaxy and WebGestalt. Additionally, the Sequence Read Archive (SRA) was established as a public repository for next-generation sequence data, as was the use of the Gene Expression Omnibus (GEO) functional genomic data repository. In this work, using total RNA sequencing analysis, it was possible to demonstrate generalized comparisons of early-stage CM with recurrent CM. Furthermore, Gene Ontology (GO), KEGG and Reactome were used to evaluate the functional relationships and improved pathways between early-stage CM and post-mastectomy recurrent CM. In conclusion, through the development of this study it was possible to discover new biomarkers that could be used as future therapeutic targets, enabling a better diagnosis and prognosis in BC aiming to improve the overall survival of patients.El cáncer de mama (CM) es una enfermedad altamente prevalente en las mujeres con millones de casos nuevos cada año. Entre los avances tecnológicos destaca la tecnología RNA-seq, que ha permitido comprender mejor la expresión génica, permitiendo desvelar interacciones proteicas entre tumores de mama tempranos y recurrentes (posmastectomía). Han surgido nuevas herramientas basadas en bioinformática para seguir el avance de la secuenciación, siendo los principales ejemplos las plataformas de análisis online Galaxy y WebGestalt. Además, se estableció el Archivo de lectura de secuencias (SRA) como un depósito público para datos de secuencias de próxima generación, al igual que el uso del depósito de datos genómicos funcionales Gene Expression Omnibus (GEO). En este trabajo, utilizando el análisis de secuenciación de ARN total, fue posible demostrar comparaciones generalizadas de CM en etapa temprana con CM recurrente. Además, se utilizaron Gene Ontology (GO), KEGG y Reactome para evaluar las relaciones funcionales y las vías mejoradas entre la CM en etapa temprana y la CM recurrente posmastectomía. En conclusión, gracias al desarrollo de este estudio fue posible descubrir nuevos biomarcadores que podrían ser utilizados como futuras dianas terapéuticas, permitiendo un mejor diagnóstico y pronóstico en CM con el objetivo de mejorar la supervivencia global de los pacientes.O câncer/neoplasias de mama (CM) é uma doença altamente incidente em mulheres com milhões de novos casos a cada ano. Dentre os avanços tecnológicos destaca-se a tecnologia de RNA-seq que permitiu compreender melhor a expressão gênica, possibilitando desvendar as interações proteicas entre tumores de mama em estágio inicial e recorrente (pós-mastectomia). Novas ferramentas baseadas em bioinformática surgiram para acompanhar o avanço dos sequenciamentos, e tem-se como principais exemplos as plataformas online de análise Galaxy e WebGestalt. Além disso, foi estabelecido o Sequence Read Archive (SRA) como um repositório público para os dados de sequência de nova geração, assim como foi estabelecido o uso do repositório de dados genômicos funcionais o Gene Expression Omnibus (GEO). Neste trabalho, utilizando análise de sequenciamento de RNA total, foi possível demonstrar comparações generalizadas do CM em um estágio inicial com CM recorrente. Além disso, utilizou-se Ontologia Genética (GO), KEGG e Reactome para avaliar as relações funcionais e vias aprimoradas entre CM em um estágio inicial e CM recorrente pós-mastectomia. Em conclusão, através do desenvolvimento deste estudo foi possível descobrir novos biomarcadores que poderão ser utilizados como futuros alvos terapêuticos, possibilitando um melhor diagnóstico e prognóstico no CM visando à melhoria da sobrevida global das pacientes.O câncer/neoplasias de mama (CM) é uma doença altamente incidente em mulheres com milhões de novos casos a cada ano. Dentre os avanços tecnológicos destaca-se a tecnologia de RNA-seq que permitiu compreender melhor a expressão gênica, possibilitando desvendar as interações proteicas entre tumores de mama em estágio inicial e recorrente (pós-mastectomia). Novas ferramentas baseadas em bioinformática surgiram para acompanhar o avanço dos sequenciamentos, e tem-se como principais exemplos as plataformas online de análise Galaxy e WebGestalt. Além disso, foi estabelecido o Sequence Read Archive (SRA) como um repositório público para os dados de sequência de nova geração, assim como foi estabelecido o uso do repositório de dados genômicos funcionais o Gene Expression Omnibus (GEO). Neste trabalho, utilizando análise de sequenciamento de RNA total, foi possível demonstrar comparações generalizadas do CM em um estágio inicial com CM recorrente. Além disso, utilizou-se Ontologia Genética (GO), KEGG e Reactome para avaliar as relações funcionais e vias aprimoradas entre CM em um estágio inicial e CM recorrente pós-mastectomia. Em conclusão, através do desenvolvimento deste estudo foi possível descobrir novos biomarcadores que poderão ser utilizados como futuros alvos terapêuticos, possibilitando um melhor diagnóstico e prognóstico no CM visando à melhoria da sobrevida global das pacientes

Computational biology helps understand how polyploid giant cancer cells drive tumor success

Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. Newly formed cells end up accessing numerous multicellular and unicellular programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal or diverse clone formation. An integrative literature review was carried out, searching articles in several sites, including: PUBMED, NCBI-PMC, and Google Academic, published in English, indexed in referenced databases and without a publication time filter, but prioritizing articles from the last 3 years, to answer the following questions: (i) “What is the current knowledge about polyploidy in tumors?”; (ii) “What are the applications of computational studies for the understanding of cancer polyploidy?”; and (iii) “How do PGCCs contribute to tumorigenesis?

Imatinib resistance

The development of point mutations in the BCR-ABL kinase domain is the main reason for imatinib resistance in chronic myeloid leukemia. Different detection methods are used in chronic myeloid leukemia monitoring, such as direct sequencing, denaturing high performance liquid chromatography and allele specific polymerase chain reaction. Mutation analysis has become mandatory during patient workup of chronic myeloid leukemia in order for the physician to choose the most suitable tyrosine kinase inhibitor. This article, a review of possible therapies used to overcome imatinib resistance, investigates the current position by searching the PubMed electronic database using the following keywords: imatinib, dasatinib, nilotinib, aurora kinase, SRC kinase, mutation, treatment, drugs and resistance. New tyrosine kinase inhibitors include BCR-ABL kinase selective inhibitors, dual ABL/SRC kinase inhibitors and aurora kinase inhibitors. Awareness of the spectrum of new drugs against mutations, in particular the T315I mutation, makes it possible to properly select the best therapy for each patient

FADS1 and FADS2 Gene Polymorphisms Modulate the Relationship of Omega-3 and Omega-6 Fatty Acid Plasma Concentrations in Gestational Weight Gain: A NISAMI Cohort Study

The polymorphisms of fatty acid desaturase genes FADS1 and FADS2 have been associated with an increase in weight gain. We investigated FADS1 and FADS2 gene polymorphisms and the relation between ω-3 and ω-6 fatty acid plasma concentrations and gestational weight gain. A prospective cohort study of 199 pregnant women was followed in Santo Antônio de Jesus, Brazil. Plasma levels of polyunsaturated fatty acids (PUFAs) were measured at baseline and gestational weight gain during the first, second, and third trimesters. Fatty acid recognition was carried out with the aid of gas chromatography. Single nucleotide polymorphisms (SNPs) were genotyped using real-time PCR. Statistical analyses included Structural Equation Modelling. A direct effect of FADS1 and FADS2 gene polymorphisms on gestational weight was observed; however, only the SNP rs174575 (FADS2) showed a significant positive direct effect on weight over the course of the pregnancy (0.106; p = 0.016). In terms of the influence of SNPs on plasma levels of PUFAs, it was found that SNP rs174561 (FADS1) and SNP rs174575 (FADS2) showed direct adverse effects on plasma concentrations of ω-3 (eicosapentaenoic acid and alpha-linoleic acid), and only SNP rs174575 had positive direct effects on plasma levels of ARA and the ARA/LA (arachidonic acid/linoleic acid) ratio, ω-6 products, while the SNP rs3834458 (FADS2) had an adverse effect on plasma concentrations of EPA, leading to its increase. Pregnant women who were heterozygous and homozygous for the minor allele of the SNP rs3834458 (FADS2), on the other hand, showed larger concentrations of series ω-3 substrates, which indicates a protective factor for women’s health

Polymorphisms in methylenetetrahydrofolate reductase and cystathionine beta-synthase in oral cancer - a case-control study in southeastern Brazilians

ABSTRACT INTRODUCTION: Oral squamous cell carcinoma (OSCC) is a serious public health problem, due to its high mortality rate and worldwide rising incidence. OSCC susceptibility is mediated by interactions between genetic and environmental factors. Studies suggest that genetic variants encoding enzymes involved in folate metabolism may modulate OSCC risk by altering DNA synthesis/repair and methylation process. OBJECTIVE: The goals of this study were to evaluate the association of three genotypic polymorphism (MTHFR C677T, MTHFR A1298C and CBS 844ins68) and oral cancer risk in southeastern Brazilians and evaluate the interactions between polymorphisms and clinical histopathological parameters. METHODS: This case-control study included 101 cases and 102 controls in the state of Espírito Santo, Brazil. MTHFR genotyping was done by PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism) and CBS genotyping by PCR (polymerase chain reaction) analysis. RESULTS: MTHFR C677T polymorphism was associated with lymph node involvement. Genotype CT + TT acted as a protective factor. MTHFR A1298C AC + CC genotype was associated with tumor differentiation, and possibly with a better prognosis. In risk analysis, no correlation was observed between genotypes and OSCC. CONCLUSION: We concluded that MTHFR C677T, MTHFR A1298C and CBS 844ins68 polymorphisms were not associated with OSCC risk in southeastern Brazilians; however, we suggest a prognosis effect associated with MTHFR C677T and A1298C polymorphisms in OSCC

HIF1-alpha expression predicts survival of patients with squamous cell carcinoma of the oral cavity.

BACKGROUND: Oral squamous cell carcinoma is an important cause of death and morbidity wordwide and effective prognostic markers are still to be discovered. HIF1α protein is associated with hypoxia response and neovascularization, essential conditions for solid tumors survival. The relationship between HIF1α expression, tumor progression and treatment response in head and neck cancer is still poorly understood. PATIENTS AND METHODS: In this study, we investigated HIF1α expression by immunohistochemistry in tissue microarrays and its relationship with clinical findings, histopathological results and survival of 66 patients with squamous cell carcinoma of the lower mouth. RESULTS: Our results demonstrated that high HIF1α expression is associated with local disease-free survival, independently from the choice of treatment. Furthermore, high expression of HIF1α in patients treated with postoperative radiotherapy was associated with survival, therefore being a novel prognostic marker in squamous cell carcinoma of the mouth. Additionally, our results showed that MVD was associated with HIF1α expression and local disease relapse. CONCLUSION: These findings suggest that HIF1α expression can be used as a prognostic marker and predictor of postoperative radiotherapy response, helping the oncologist choose the best treatment for each patient

Genetic variability of inflammatory genes in the brazilian population

Inflammatory gene variants have been associated with several diseases, including cancer, diabetes, vascular diseases, neurodegenerative diseases, arthritis, and others. Therefore, determining the population genetic composition of inflammation-related genes can be useful for the determination of general risk, prognostic and therapeutic strategies to prevent or cure specific diseases. We have aimed to identify polymorphism genotype frequencies in genes related to the inflammatory response in the Brazilian population, namely, IjBL - 62AT, IjBL - 262CT, tumor necrosis factors alpha (TNFa) - 238GA, TNFa - 308GA, lymphotoxin-alpha (LTa) + 80AC, LTa + 252AG, FAS - 670AG, and FASL - 844TC, considering the white, black, and Pardo ethnicities of the Sa˜o Paulo State. Our results suggest that the Brazilian population is under a miscegenation process at the current time, since some genotypes are not in the Hardy–Weinberg equilibrium. In addition, we conclude that the Pardo ethnicity is derived from a complex mixture of ethnicities, including the native Indian population