RESUMO
Fighting cancer remains one of the greatest challenges for science in the 21st century. Advances in immunotherapy against different types of cancer have greatly contributed to the treatment, remission, and cure of patients. In this context, knowledge of epigenetic phenomena, their relationship with tumor cells and how the immune system can be epigenetically modulated represent some of the greatest advances in the development of anticancer therapies. Epigenetics is a rapidly growing field that studies how environmental factors can affect gene expression without altering DNA sequence. Epigenomic changes include DNA methylation, histone modifications, and non-coding RNA regulation, which impact cellular function. Epigenetics has shown promise in developing cancer therapies, such as immunotherapy, which aims to stimulate the immune system to attack cancer cells. For example, PD-1 and PD-L1 are biomarkers that regulate the immune response to cancer cells and recent studies have shown that epigenetic modifications can affect their expression, potentially influencing the efficacy of immunotherapy. New therapies targeting epigenetic modifications, such as histone deacetylases and DNA methyltransferases, are being developed for cancer treatment, and some have shown promise in preclinical studies and clinical trials. With growing understanding of epigenetic regulation, we can expect more personalized and effective cancer immunotherapies in the future. This review highlights key advances in the use of epigenetic and epigenomic tools and modern immuno-oncology strategies to treat several types of tumors.
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PURPOSE: This study described and compared the oral characteristics of Brazilian individuals with mucopolysaccharidosis (MPS) and without MPS. METHODS: A cross-sectional study was performed with 29 individuals with MPS and 29 without MPS and their parents/guardians. The individuals were aged between 3 and 21 years and attended at two hospitals in Belo Horizonte, southeastern Brazil. The dental characteristics were evaluated by clinical examination of dental caries, gingivitis, malocclusion, dental anomalies and developmental defects of enamel. The parents/guardians answered a questionnaire about the sociodemographic and behavioural aspects of their children. The study was approved by the Research Ethics Committee of the Federal University of Minas Gerais. RESULTS: The average age of the individuals was 13.9 years (± 7.2). The majority were male (58.6%), had black/brown skin (70.7%) and were from favored economic class (89.7%). Dental caries, gingivitis, malocclusion and dental anomalies were more prevalent in the MPS group (p < 0.05). CONCLUSION: The individuals with MPS had a higher prevalence of oral diseases and dental anomalies than the group without MPS.
Assuntos
Cárie Dentária , Má Oclusão , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Cárie Dentária/epidemiologia , Humanos , Masculino , Saúde Bucal , Prevalência , Qualidade de Vida , Inquéritos e Questionários , Adulto JovemRESUMO
The constant demand for new antibiotic drugs has driven efforts by the scientific community to prospect for peptides with a broad spectrum of action. In this context, antimicrobial peptides (AMPs) have acquired great scientific importance in recent years due to their ability to possess antimicrobial and immunomodulatory activity. In the last two decades, plants have attracted the interest of the scientific community and industry as regards their potential as biofactories of heterologous proteins. One of the most promising approaches is the use of viral vectors to maximize the transient expression of drugs in the leaves of the plant Nicotiana benthamiana. Recently, the MagnifectionTM expression system was launched. This sophisticated commercial platform allows the assembly of the viral particle in leaf cells and the systemic spread of heterologous protein biosynthesis in green tissues caused by Agrobacterium tumefaciens "gene delivery method". The system also presents increased gene expression levels mediated by potent viral expression machinery. These characteristics allow the mass recovery of heterologous proteins in the leaves of N. benthamiana in 8 to 10 days. This system was highly efficient for the synthesis of different classes of pharmacological proteins and contains enormous potential for the rapid and abundant biosynthesis of AMPs.
Assuntos
Agrobacterium tumefaciens/metabolismo , Peptídeos Catiônicos Antimicrobianos/biossíntese , Agricultura Molecular/métodos , Nicotiana/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Biossíntese de Proteínas , Peptídeos Catiônicos Antimicrobianos/farmacologia , Biotecnologia/métodos , Vetores Genéticos/genética , Vetores Genéticos/metabolismoRESUMO
Despite the advances in tumor identification and treatment, cancer remains the primary driver of death around the world. Also, regular treatments for the disease are incapable of targeting particular cancer types at different stages since they are not specifically focused on harmful cells since they influence both solid and tumor cells, causing side effects and undesirable symptoms. Therefore, novel strategies should be developed to treat this disease. Several efforts have been made in this direction to find more effective alternatives to cancer treatment, such as the use of antimicrobial peptides (AMPs) with antitumoral activity, nanocarriers and natural compounds from a variety of sources. AMPs are more specific to their targets because of electrostatic interaction between AMPs and the cancer cells' plasma membrane. Nanocarriers may be used for the delivery of non-soluble drugs, which are poorly stable or require a controlled release. In addition, natural compounds have been a rich source of anti-cancer agents for decades. In this review, these three approaches will be discussed, showing recent advances and advantages of using these strategies to treat cancer as well as the combination of these approaches increasing anticancer activity.
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Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Humanos , NanotecnologiaRESUMO
Improving the quality and performance of soybean oil as biodiesel depends on the chemical composition of its fatty acids and requires an increase in monounsaturated acids and a reduction in polyunsaturated acids. Despite its current use as a source of biofuel, soybean oil contains an average of 25 % oleic acid and 13 % palmitic acid, which negatively impacts its oxidative stability and freezing point, causing a high rate of nitrogen oxide emission. Gas chromatography and ion mobility mass spectrometry were conducted on soybean fatty acids from metabolically engineered seed extracts to determine the nature of the structural oleic and palmitic acids. The soybean genes FAD2-1 and FatB were placed under the control of the 35SCaMV constitutive promoter, introduced to soybean embryonic axes by particle bombardment and down-regulated using RNA interference technology. Results indicate that the metabolically engineered plants exhibited a significant increase in oleic acid (up to 94.58 %) and a reduction in palmitic acid (to <3 %) in their seed oil content. No structural differences were observed between the fatty acids of the transgenic and non-transgenic oil extracts.
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Ácidos Graxos/química , Glycine max/química , Plantas Geneticamente Modificadas/química , Sementes/química , Engenharia Metabólica , Plantas Geneticamente Modificadas/genética , Sementes/genética , Óleo de Soja/química , Óleo de Soja/genética , Óleo de Soja/metabolismo , Glycine max/genéticaRESUMO
Plants have emerged as an attractive alternative to the traditional mammalian cell cultures or microbial cell-based systems system for the production of valuable recombinant proteins. Through recombinant DNA technology, plants can be engineered to produce large quantities of pharmaceuticals and industrial proteins of high quality at low costs. The recombinant production, by transgenic plants, of therapeutic proteins normally present in human plasma, such as cytokines, coagulation factors, anticoagulants, and immunoglobulins, represents a response to the ongoing challenges in meeting the demand for therapeutic proteins to treat serious inherited or acquired bleeding and immunological diseases. As the clinical utilization of fractionated plasma molecules is limited by high production costs, using recombinant biopharmaceuticals derived from plants represents a feasible alternative to provide efficient treatment. Plant-derived pharmaceuticals also reduce the potential risks to patients of infection with pathogens or unwanted immune responses due to immunogenic antigens. In this review, we summarize the recent advances in molecular farming of cytokines. We also examine the technological basis, upcoming challenges, and perspectives for the biosynthesis and detection of these molecules in different plant production platforms.
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Citocinas/genética , Agricultura Molecular , Plantas Geneticamente Modificadas/metabolismo , Proteínas Recombinantes/genética , Produtos Biológicos , Proteínas Sanguíneas/genética , Humanos , Engenharia de Proteínas , Tecnologia Farmacêutica/métodosRESUMO
Seeds are organs specialised in accumulating proteins, and they may provide a potential economically viable platform for the large-scale production and storage of many molecules for pharmaceutical and other productive sectors. Soybean [Glycine max (L.) Merrill] has a high seed protein content and represents an excellent source of abundant and cheap biomass. Under greenhouse conditions and a daily photoperiod of 23 h of light, the soybean plant's vegetative growth can be significantly extended by inducing more than a tenfold increase in seed production when compared with plants cultivated under field conditions. Some factors involved in the production of different recombinant proteins in soybean seeds are discussed in this review. These include transgenic system, regulatory sequences and the use of Mass Spectrometry as a new tool for molecular characterisation of seed produced recombinant proteins. The important intrinsic characteristics and possibility of genetically engineering soybean seeds, using current advances in recombinant DNA technology including metabolic engineering and synthetic biology, should form the foundation for large-scale and more precise genome modification, making this crop an important candidate as bioreactor for production of recombinant molecules.
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Glycine max/genética , Proteínas Recombinantes/genética , Proteínas de Soja/genética , Animais , Engenharia Genética/métodos , Genoma de Planta , Humanos , Espectrometria de Massas , Agricultura Molecular/métodos , Sementes , Glycine max/crescimento & desenvolvimento , Glycine max/metabolismo , TransgenesRESUMO
The seed-based production of recombinant proteins is an efficient strategy to achieve the accumulation, correct folding, and increased stability of these recombinant proteins. Among potential plant molecular farming systems, soybean [Glycine max (L.) Merrill] is a viable option for the production of recombinant proteins due to its high protein content, known regulatory sequences, efficient gene transfer protocols, and a scalable production system under greenhouse conditions. We report here the expression and stable accumulation of human coagulation factor IX (hFIX) in transgenic soybean seeds. A biolistic process was utilised to co-introduce a plasmid carrying the hFIX gene under the transcriptional control of the α' subunit of a ß-conglycinin seed-specific promoter and an α-Coixin signal peptide in soybean embryonic axes from mature seeds. The 56-kDa hFIX protein was expressed in the transgenic seeds at levels of up to 0.23% (0.8 g kg(-1) seed) of the total soluble seed protein as determined by an enzyme-linked immunosorbent assay (ELISA) and western blot. Ultrastructural immunocytochemistry assays indicated that the recombinant hFIX in seed cotyledonary cells was efficiently directed to protein storage vacuoles. Mass spectrometry characterisation confirmed the presence of the hFIX recombinant protein sequence. Protein extracts from transgenic seeds showed a blood-clotting activity of up to 1.4% of normal plasma. Our results demonstrate the correct processing and stable accumulation of functional hFIX in soybean seeds stored for 6 years under room temperature conditions (22 ± 2°C).
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Fator IX/metabolismo , Glycine max/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Proteínas Recombinantes/metabolismo , Sequência de Aminoácidos , Antígenos de Plantas/genética , Coagulação Sanguínea/efeitos dos fármacos , Fator IX/genética , Fator IX/farmacologia , Globulinas/genética , Humanos , Dados de Sequência Molecular , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Regiões Promotoras Genéticas , Sinais Direcionadores de Proteínas/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Proteínas de Armazenamento de Sementes/genética , Sementes/genética , Sementes/metabolismo , Proteínas de Soja/genética , Glycine max/genéticaRESUMO
We produced human growth hormone (hGH), a protein that stimulates growth and cell reproduction, in genetically engineered soybean [Glycine max (L.) Merrill] seeds. Utilising the alpha prime (α') subunit of ß-conglycinin tissue-specific promoter from soybean and the α-Coixin signal peptide from Coix lacryma-jobi, we obtained transgenic soybean lines that expressed the mature form of hGH in their seeds. Expression levels of bioactive hGH up to 2.9% of the total soluble seed protein content (corresponding to approximately 9 g kg(-1)) were measured in mature dry soybean seeds. The results of ultrastructural immunocytochemistry assays indicated that the recombinant hGH in seed cotyledonary cells was efficiently directed to protein storage vacuoles. Specific bioassays demonstrated that the hGH expressed in the soybean seeds was fully active. The recombinant hGH protein sequence was confirmed by mass spectrometry characterisation. These results demonstrate that the utilisation of tissue-specific regulatory sequences is an attractive and viable option for achieving high-yield production of recombinant proteins in stable transgenic soybean seeds.
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Glycine max/genética , Hormônio do Crescimento Humano/biossíntese , Plantas Geneticamente Modificadas/genética , Proteínas Recombinantes/biossíntese , Sementes/genética , Sequência de Aminoácidos , Antígenos de Plantas/genética , Globulinas/genética , Hormônio do Crescimento Humano/genética , Humanos , Dados de Sequência Molecular , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/metabolismo , Regiões Promotoras Genéticas , Sinais Direcionadores de Proteínas/genética , Proteínas Recombinantes/genética , Proteínas de Armazenamento de Sementes/genética , Sementes/metabolismo , Proteínas de Soja/genética , Glycine max/metabolismo , Vacúolos/metabolismoRESUMO
Human factor IX is synthesized in the liver and secreted in the blood, where it participates in a group of reactions involving coagulation factors and proteins that permit sanguinary coagulation. In this work two lines of transgenic mice were developed to express the FIX gene in the mammalian glands under control of milk beta-casein promoter. The founding females secreted the FIX in their milk (3% total soluble protein). The stable integration of transgene was confirmed by southern blot analysis. The presence of the FIX recombinant protein in the milk of transgenic females was confirmed by western blot and the clotting activity was revealed in blood-clotting assays. The coagulation activity in human blood treated with recombinant FIX increased while the time of coagulation decreased. Our results confirm the production of a large amount of recombinant biologically active FIX in the mammary gland of transgenic mice.
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Fator IX/biossíntese , Glândulas Mamárias Animais/metabolismo , Proteínas do Leite/biossíntese , Animais , Southern Blotting , Western Blotting , Fator IX/metabolismo , Fator IX/fisiologia , Feminino , Lactação , Masculino , Camundongos , Camundongos Transgênicos , Proteínas do Leite/genética , Proteínas do Leite/metabolismo , Tempo de Tromboplastina Parcial , Reação em Cadeia da Polimerase , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/metabolismoRESUMO
A cross-sectional survey was carried out. This involved 652 out of a total of 764 (85%) 13-year-old adolescents enrolled in private and public schools located in urban areas in Cianorte, Brazil. They were interviewed and examined for traumatic dental injuries by one trained examiner (B.N.) using validated criteria. Sociodemographic data included sex, family structure (nuclear families, single parents and step-parents) and socio-economic indicators. Anthropometric measures included height and weight. The body mass index (BMI) was calculated (mean=20.1; SD=3.7). Those who had BMI scores equal or above the 85% percentile were considered overweight (BMI >23). The prevalence of traumatic injuries to the permanent incisors was 20.4%. The most common reported cause of injuries to the permanent incisors was falls (24.1%) followed by collisions with people or inanimate objects (15%), traffic accidents (10.5%), misuse of the teeth (6%), sports (2.3%) and violence (1.5%). Unknown causes accounted for 40.6%. Children from non-nuclear families, overweight children and boys were 2.18, 1.93 and 2.19 times respectively more likely to have dental injuries than children from nuclear families, non-overweight children and girls (P<0.01) after adjusting for family structure, BMI, sex, family income and level of education of the parents. The relationship between dental injuries and socioeconomic indicators was not statistically significant. In conclusion, being from a non-nuclear family, overweight and a boy increased the risk of having traumatic dental injury, but the relationship with socio-economic indicators was not statistically significant.