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1.
Braz. J. Pharm. Sci. (Online) ; 58: e18984, 2022. graf
Article in English | LILACS | ID: biblio-1364429

ABSTRACT

Interferon-ß-1a (INF-ß-1a) has gained significant attention due to its emerging applications in the treatment of different human diseases. Therefore, many researchers have attempted to produce it in large quantities and also in a biologically active form using different expression systems. In the present study, we aimed to improve the expression level of INF-ß-1a by Pichia pastoris using optimization of culture conditions. The codon-optimized INF-ß- 1a gene was cloned into pPICZαA plasmid under the control of alcohol oxidase I (AOX1) promoter. The protein expression was induced using different concentrations of methanol at different pHs and temperatures. The biological activity of produced protein was evaluated by anti-proliferative assay. The ideal culture conditions for the expression of INF-ß-1a by P. pastoris were found to be induction with 2% methanol at pH 7.0 culture medium at 30 C which yielded a concentration of 15.5 mg/L INF-ß-1a in a shake flask. Our results indicate that differences in glycosylation pattern could result in different biological activities as INF- ß-1a produced by P. pastoris could significantly more reduce the cell viability of HepG-2 cells, a hepatocellular carcinoma cell line, than a commercially available form of this protein produced by CHO


Subject(s)
Pichia/classification , Interferon-beta/agonists , Carcinoma, Hepatocellular/pathology , Process Optimization , Codon , Cells , Carcinoma, Hepatocellular , Hydrogen-Ion Concentration
2.
Rev. colomb. anestesiol ; 49(2): e501, Apr.-June 2021. graf
Article in English | LILACS, COLNAL | ID: biblio-1251503

ABSTRACT

Abstract Introduction Neuropathic pain is present in up to 40 % of all cancer patients. A considerable number of patients fail to achieve enough pain relief with conventional treatment, which is why therapeutic alternatives such as spinal cord stimulation should be considered. Case description and results This is the case of a female patient with chronic neuropathic pain secondary to a partial femoral nerve injury sustained during resection and lymph node dissection surgery with curative intent for a large stage II cell squamous cell carcinoma T2N0M0, localized in the right popliteal fossa. The patient presented with difficult to manage chronic neuropathic pain, despite receiving multiple oral analgesics and nerve blocks. A medullary neurostimulator was implanted that relieved the patient's pain intensity in up to 80%, in addition to improved function and quality of life. Conclusions Spinal cord stimulation is considered an effective neuromodulatory intervention which has shown satisfactory results in the treatment of various types of refractory chronic pain in cancer patients, including neuropathic pain.


Resumen Introducción El dolor neuropático está presente hasta en el 40 % de los pacientes con cáncer. Un número considerable de pacientes no logran un alivio suficiente del dolor con el tratamiento convencional, por lo cual deben considerarse alternativas terapéuticas como la estimulación de la médula espinal. Descripción del caso y resultados Caso de una paciente con dolor neuropático crónico secundario a lesión parcial de nervio femoral durante cirugía de resección y vaciamiento ganglionar con objetivos curativos de carcinoma escamocelular de célula grande T2N0M0 estadio II, localizado en la fosa poplítea derecha, quien cursó con dolor neuropático crónico de difícil manejo a pesar de recibir múltiples analgésicos orales y bloqueos nerviosos. Se implantó un neuroestimulador medular con lo cual se logró un alivio hasta del 80 % en intensidad de dolor de la paciente, además de una mejoría de su funcionalidad y calidad de vida. Conclusiones La estimulación de la médula espinal se considera una intervención neuromoduladora eficaz, que ha demostrado resultados satisfactorios para tratar diversas formas de dolor crónico refractario en los pacientes con cáncer, incluido el dolor neuropático.


Subject(s)
Humans , Female , Middle Aged , Carcinoma, Squamous Cell , Chronic Pain , Pain Management , Spinal Cord Stimulation , Lymph Node Excision , Neoplasms , Quality of Life , Therapeutics , Cells , Femoral Nerve , Analgesics , Nerve Block , Neuralgia
3.
Rev. argent. cir ; 113(1): 121-124, abr. 2021. graf
Article in Spanish | LILACS, BINACIS | ID: biblio-1288182

ABSTRACT

RESUMEN La neoplasia papilar intracolecística con carcinoma mucinoso invasor y células en anillo de sello es una variedad de cáncer de vesícula, una patología agresiva y con mal pronóstico, la cual puede presentarse en forma similar a una colecistitis y, a pesar del tratamiento operatorio y quimioterapia posterior, la supervivencia y pronóstico son peores en relación con los otros cánceres de vesícula. Este artículo tie ne por objetivo describir un tipo histológico muy específico, de baja frecuencia, de cáncer de vesícula y el tratamiento realizado.


ABSTRACT Intracholecystic papillary neoplasm with invasive mucinous adenocarcinoma and signet ring cells is a rare, aggressive variety of gallbladder cancer, with symptoms mimicking cholecystitis. Survival and prognosis are worse that other types of gallbladder cancer despite surgery and chemotherapy. The aim of this article is to describe a case of a rare gallbladder cancer with specific histology and the treatment performed


Subject(s)
Humans , Male , Aged , Gallbladder Neoplasms , Pathology , Survival , Therapeutics , Grief , Cells , Baja , Blister , Drug Therapy , Gallbladder , Histology , Neoplasms
4.
Gac. méd. boliv ; 43(2): 179-183, dic. 2020. ilus
Article in Spanish | LILACS | ID: biblio-1249981

ABSTRACT

El artículo se centra en la utilización de la nueva herramienta, CRISPR (repeticiones palindrómicas cortas agrupadas a intervalos regulares), la cual permite editar los genomas de los seres vivos de manera más precisa que otras técnicas; a lo largo del artículo se mencionan trabajos relacionados con la detención de la angiogénesis, cáncer, Sarcoma de Kaposi en inmunodeficiencias, Parkinson, regeneración y modificación genética en humanos, todas estas investigaciones tiene en común la utilización de la herramienta CRISPR. También se comenta las complicaciones éticas que conlleva utilizar esta tecnología en el ADN de células embrionarias humanas, que según diferentes criterios, podrían llevar a generar seres humanos “mejorados”, es decir no solo sin susceptibilidad a enfermedades degenerativas o incurables, sino también modificados en aspectos físicos que no necesariamente estarían ligados a alguna patología.


The article focuses on the use of the new tool, CRISPR (short palindromic repetitions grouped at regular intervals), which allows editing the genomes of living beings more accurately than other techniques; Throughout the article, works related to the arrest of angiogenesis, cancer, Kaposi’s sarcoma in immunodeficiencies, Parkinson’s, regeneration and genetic modification in humans are mentioned, all these investigations have in common the use of the CRISPR tool. You can also comment on the ethical complications that involve using this technology in the DNA of human embryonic cells, which according to different criteria, carry out improved human beings, that is not only without susceptibility to degenerative or incurable diseases, but also modified in physical aspects that are not linked to any pathology.


Subject(s)
DNA , Clustered Regularly Interspaced Short Palindromic Repeats , Sarcoma, Kaposi , Cells , Genome , Genetics , Neoplasms
5.
Acta bioquím. clín. latinoam ; 54(3): 321-331, set. 2020. ilus, graf
Article in Spanish | LILACS | ID: biblio-1130606

ABSTRACT

Los flavivirus transmitidos por mosquitos son una amenaza actual y emergente en todo el mundo. Dentro de este género, el virus Encefalitis San Luis (VESL) causa una forma severa de enfermedad neuroinvasiva donde la respuesta inmune es un componente crucial de la defensa del huésped. En este trabajo se investigó la interacción entre VESL y células de la inmunidad innata, en un modelo de infección in vitro de monocitos humanos (células U937) con cepas de distinta virulencia y condiciones epidemiológicas de aislamiento (CbaAr-4005 y 78V-6507). Se evaluó la capacidad de infectar y replicar del virus, como también el efecto citopático y la cinética de viabilidad de monocitos durante la infección. Los resultados demostraron la susceptibilidad de los monocitos a la infección, replicación y muerte por ambas cepas virales. Sin embargo, se hallaron diferencias significativas entre ellas. La cepa epidémica y de mayor virulencia CbaAr-4005 registró una tasa de infección y replicación superior a la de la cepa endémica y de menor virulencia 78V-6507. Se comprobó también que el VESL indujo la muerte de monocitos humanos, dependiendo del tiempo post-infección (pi) y de la cepa. Así, CbaAr-4005 provocó a partir del día 3 pi el doble de mortalidad celular que 78V-6507. Además, en los monocitos infectados se observaron alteraciones de parámetros morfológicos que podrían relacionarse con el tipo de mecanismo de muerte celular asociado a la infección por VESL.


Mosquitoes borne Flavivirus infections are an actual and emergent worldwide threat to human health. Within this genus, Saint Louis Encephalitis Virus (SLEV) causes a severe neuroinvasive disease where immune response is crucial for host survival. In this study the interaction between SLEV and innate immune cells was evaluated. An in vitro infection model with human monocytes (U937 cells) and strains with variations in virulence and isolation conditions (CbaAr-4005 and 78V-6507) were used. Infection capacity, replication capacity, cytopathic effect and monocyte viability kinetics were measured. The results showed susceptibility to infection and replication to both strains. However, significant differences were found among them. CbaAr-4005, the epidemic and more virulent strain, showed higher infection and replication ratios compared to 78V-6507. SLEV infection that induces cell death of human monocytes was also found in a post-infection time and in a strain dependent manner. Since day 3 post-infection, twice the mortality in CbaAr-4005 infected cells was observed. Furthermore, infected monocytes showed alterations in morphologic parameters that could be related with apoptosis mechanisms associated to SLEV infections.


Os Flavivírus transmitidos por mosquitos são uma ameaça atual e emergente no mundo todo. Nesse gênero, o vírus Encefalite Saint Louis (VESL) causa uma forma grave de doença neuroinvasiva onde a resposta imune é um componente crucial da defesa do hospedeiro. Neste trabalho nos investigamos a interação entre VESL e células de imunidade inata em um modelo de infecção in vitro de monócitos humanos (células U937) com estirpe de diferentes virulências e condições epidemiológicas de isolamento (CbaAr-4005 e 78V-6507). Foi avaliada a capacidade do vírus de infectar e replicar , assim como o efeito citopático e a viabilidade cinética dos monócitos durante a infecção. Os resultados demonstraram a suscetibilidade dos monócitos à infecção, replicação e morte por ambas as estirpes virais. No entanto, foram detectadas diferenças significativas entre eles. A estirpe epidémica e de maior virulenta CbaAr-4005 teve uma maior taxa de infecção e replicação do que a estirpe endémica e menos virulenta 78V-6507. Foi comprovado também que o VESL induziu a morte de monócitos humanos, dependendo do tempo pós-infecção (pi) e da estirpe. Assim, a CbaAr-4005 causou a partir do dia 3 pi o dobro da mortalidade celular o que a 78V- 6507. Além disso, alterações nos parâmetros morfológicos foram observadas nos monócitos infectados que poderiam estar relacionadas ao tipo de mecanismo de morte celular associado à infecção pelo VESL.


Subject(s)
Humans , Male , Female , Virulence , Flavivirus Infections , U937 Cells , Encephalitis , Encephalitis Virus, St. Louis , Encephalitis Viruses/growth & development , Flavivirus , Patient Isolation , Viruses , In Vitro Techniques , Kinetics , Cells , Disease , Incidence , Causality , Mortality , Apoptosis , Reference Parameters , Culicidae
6.
Rev. medica electron ; 42(4): 2049-2065,
Article in Spanish | LILACS, CUMED | ID: biblio-1139295

ABSTRACT

RESUMEN Las células de la cresta neural son pluripotenciales y son llamadas la cuarta hoja germinativa del embrión. Con el objetivo de estructurar los referentes teóricos actualizados que sustenten la afirmación precedente y que constituirá material de estudio para los estudiantes de las Ciencias Médicas, se realizó la revisión de 28 referencias bibliográficas, de ellas 89% actualizadas. Estas células aparecen durante la neurulación y pasado este proceso transitan de epitelial a mesenquimatosa; migran siguiendo señales de la matriz extracelular a todo el cuerpo del embrión diferenciándose en tejidos disimiles. Muy vinculados en su evolución a mecanismos epigenéticos, hacen a esta población celular vulnerables a ser dañadas invocándose en la etiología de diferentes defectos congénitos y enfermedades crónicas no trasmisibles como cáncer. Como conclusión por su pluripotencialidad y por los mecanismos moleculares que distinguen su evolución son consideradas por muchos autores la cuarta hoja germinativa del embrión (AU).


SUMMARY Neural crest cells are pluripotentials, and are called the fourth germinative leaf of the embryo. With the objective of structuring the updated theoretical referents backing up the precedent affirmation that will be study material for the students of Medical Sciences, the authors reviewed 28 bibliographic references, 89 % of them updated. These cells appear during neurulation and after this process they transit from epithelial to mesenchymal; following extracellular matrix signals, they migrate to the whole embryo body differentiating themselves in dissimilar tissues. Tightly related in their evolution to epigenetic mechanisms, this cell population is very likely to be damaged and so they are invoked in the etiology of different congenital defects and noncommunicable chronic diseases like cancer. In conclusion, due to their pluripotentiality and the molecular mechanisms distinguishing their evolution, many authors consider them the embryo´s fourth germinative leaf (AU).


Subject(s)
Humans , Male , Female , Cells/metabolism , Neural Crest/pathology , Students, Medical , Vertebrates/genetics , Neurulation/physiology , Neural Crest/abnormalities , Neural Crest/physiology , Neural Crest/physiopathology
7.
Rev. cuba. angiol. cir. vasc ; 21(2): e91, mayo.-ago. 2020. tab, fig
Article in Spanish | LILACS, CUMED | ID: biblio-1126380

ABSTRACT

Introducción: La enfermedad arterial oclusiva de miembros inferiores se asocia con un alto índice de amputaciones y riesgo de muerte. Al respecto, la medicina regenerativa ha mostrado resultados satisfactorios. Objetivo: Caracterizar a los pacientes con enfermedad arterial periférica de los miembros inferiores, tratados con células mononucleares autólogas. Métodos: Se realizó una investigación longitudinal prospectiva en el Hospital Universitario "Arnaldo Milián Castro", durante el período desde enero de 2015 hasta diciembre de 2017. De una población de 61 pacientes se seleccionó una muestra de 52 de forma intencional por criterios. Resultados: La edad promedio resultó de 66,9 ± 8,2 años y el 69,2 por ciento representó al sexo masculino. Los principales factores de riesgo vascular fueron el tabaquismo, la hipercolesteronemia y la hipertensión arterial. El nivel de oclusión mostró predominio fémoro poplíteo y el tractus de salida malo constituyó la principal causa de no revascularización. La viabilidad celular fue elevada y se logró cambio significativo en los estadios de Fontaine. El inicio de la mejoría clínica ocurrió entre el primer y el segundo mes en la mayoría de los casos. En una parte de los pacientes se abrieron posibilidades posquirúrgicas y se obtuvo muy buena reperfusión tisular. Conclusiones: El implante de células mononucleares autólogas en pacientes con enfermedad arterial periférica de los miembros inferiores constituye una nueva estrategia de angiogénesis terapéutica muy útil y efectiva, que abre nuevas perspectivas de tratamiento(AU)


Introduction: Low limbs´ arterial occlusive disease is associated with a high rate of amputations and risk of death. Regarding that, regenerative medicine has proven satisfactory results. Objective: To characterize patients with peripheral arterial disease in the low limbs which have been treated with autologous mononuclear cells. Methods: It was carried out a prospective longitudinal research in "Arnaldo Milián Castro" Hospital in the period from January, 2015 to December, 2017. From a population of 61 patients, it was intentionally selected by criteria a sample of 52 individuals. Results: The average age was 66,9 ± 8,2 and 69,2 percent were men. The main vascular risk factors were smoking habit, hypercholesterolemia and arterial hypertension. The level of occlusion showed predominance of femoro-popliteal and the bad output tractus was the main cause of non-revascularization. Cell viability was high and it was achieved a significant change in Fontaine stages. The beginning of a clinical improvement happened between the first and the second month in most of the cases. In some patients were open post-surgical possibilities and it was obtained great tisular reperfusion. Conclusions: The implant of autologous mononuclear cells in patients with peripheral arterial disease of low limbs represents an useful and effective new strategy of therapeutic angiogenesis which opens new treatment perspectives(AU)


Subject(s)
Humans , Middle Aged , Aged , Arterial Occlusive Diseases , Cell Survival , Cells , Lower Extremity , Regenerative Medicine
8.
Rev. cuba. hematol. inmunol. hemoter ; 36(2): e992, abr.-jun. 2020.
Article in Spanish | LILACS, CUMED | ID: biblio-1149895

ABSTRACT

Introducción: Las alteraciones cuantitativas de plaquetas son producidas por el incremento o disminución de los conteos globales de plaquetas. El incremento o trombocitosis se produce por redistribución o aumento de la producción medular; la disminución puede ser el resultado de una reducción de la producción, redistribución o acortamiento de la sobrevida de las plaquetas en circulación. Objetivo: Describir los hallazgos citomorfológicos más importantes en las alteraciones cuantitativas de plaquetas. Métodos: Se realizó una revisión de la literatura, en inglés y español, en la base de datos PubMed y el motor de búsqueda Google Académico de artículos publicados en los últimos 10 años. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: Las alteraciones cuantitativas de plaquetas se caracterizan por variaciones en el número y morfología de estas células. Estas se asocian a causas congénitas o adquiridas, en la que la detallada anamnesis de los pacientes es un elemento importante en el diagnóstico. En la trombocitosis se debe diferenciar una trombocitosis reactiva de una enfermedad medular primaria; mientras que en la trombocitopenia se debe considerar el origen étnico de los pacientes y la morfología de los leucocitos. Son numerosas las causas hereditarias de trombocitopenia con anomalías morfológicas de plaquetas y granulocitos. Conclusiones: Las alteraciones cuantitativas de plaquetas son un amplio número de entidades con semejanzas y diferencias en cuanto a presentación y manifestaciones clínicas. Los exámenes de laboratorio constituyen una herramienta importante en el diagnóstico, pronóstico y el seguimiento de los pacientes afectados(AU)


Introduction: Quantitative platelet alterations are produced by the increase or decrease in global platelet counts. Platelet count increase or thrombocytosis is produced by redistribution or increased marrow production. Platelet decrease may result from production, redistribution, or shortened survival of circulating platelets. Objective: To describe the most significant cytomorphological findings in quantitative platelet alterations. Methods: A literature review was carried out, in English and in Spanish, in the database PubMed and with the search engine of Google Scholar, of articles published in the last ten years. An analysis and summary of the revised bibliography was made. Information analysis and synthesis: Quantitative platelet alterations are characterized by variations in the number and morphology of these cells. These are associated with congenital or acquired causes, in which detailed anamnesis of patients is an important element in the diagnosis. In thrombocytosis, reactive thrombocytosis must be differentiated from primary marrow disease; while in thrombocytopenia, the ethnic origin of the patients and the morphology of the leukocytes must be considered. Hereditary causes of thrombocytopenia with morphological abnormalities of platelets and granulocytes are numerous. Conclusions: Quantitative platelet alterations are a large number of entities with similarities and differences in terms of presentation and clinical manifestations. Laboratory tests are an important tool for diagnosis, prognosis, and follow-up of affected patients(AU)


Subject(s)
Humans , Platelet Count/methods , Thrombocytopenia/diagnosis , Thrombocytosis/diagnosis , Cells/cytology , Blood Platelets/pathology
9.
Rev. méd. Chile ; 148(4): 528-534, abr. 2020. graf
Article in Spanish | LILACS | ID: biblio-1127093

ABSTRACT

Vicente Izquierdo Sanfuentes was a leading physician, researcher and academic of the School of Medicine of the University of Chile in the period 1881-1912. Dr. Izquierdo began his medical training at the Faculty of Medicine of the University of Chile (1872-1875) and then received a scholarship to continue his studies with the prominent researchers Wilhelm Hiss (1875-1877) at the University of Leipzig and Wilhelm Waldeyer at the University of Strasbourg (1877-1879) in Germany. After returning to Chile, he was appointed first professor of Histology (1881), initiating the first course of this subject in 1883. His main academic achievements and his foundational role in the origin and development of biology in Chile stand out in his work.


Subject(s)
Cells , Chile
10.
São Paulo; s.n; s.n; 2020. 133 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1292693

ABSTRACT

A regulação da fosforilação/desfosforilação das proteínas é o eixo central de muitas cascatas de sinalização. A fosfatase DUSP3, constituída apenas por um único domínio catalítico, desempenha papéis fundamentais na proliferação e senescência celular. Nas células HeLa, submetidas ao estresse genotóxico, o DUSP3 interage fisicamente com as proteínas HNRNPC, mas o efeito dessa função molecular ainda é desconhecido. Aqui demostramos que a ausência de DUPS3 mantem a proteína HNRNPC1/C2 num estado hiperfosforilado. Para entender melhor o envolvimento da interação DUSP3-HNRNPC nas funções biológicas da HNRNPC1/C2, foram estudadas células de fibroblasto deficientes de DUSP3. Foi analisado o efeito da deficiência de DUSP3 na biogênese dos ribossomos através do ensaio de perfil de polirribossomos e quantificação dos rRNAs com RT-qPCR. Os resultados mostraram que a deficiência de DUSP3 não afeta a maturação das subunidades ribossômicas, mas teria um impacto na transcrição dos pré-rRNAs e no acumulo das espécies 47S/45S. A expressado de genes contendo sequencias IRES foi analisado através do RT-qPCR e sua tradução ao longo do ciclo e em condições de estresse. Da expressão, não existe nenhuma diferença nos níveis de transcrição dos genes c-myc e xiap nas células normais e deficientes de DUSP3 em condições basais. Embora a síntese destas proteínas é maior nas células deficientes, mantendo um nível maior de tradução ao longo de todo o ciclo. Sob condições de estresse, esta duas proteínas sempre mantem uma maior expressão nas células Knockdown para DUSP3. Neste trabalho também foi estabelecido a presença de DUSP3 nos complexos da subunidade 40S, através do analise das frações obtidas do ensaio de polirribossomos e interação in vitro (Co-IP). A presença de DUSP3 nas subunidades 40S, os monossomas 80S e polissomos poderia ser através da interação direta com proteínas que possuem um domínio RRM e seria dependente dos complexos formados pelas proteínas e seus RNAs alvos. Aqui mostramos a interação in vitro de DUSP3 com a proteína PABP (com quatro domínios RRM), proteína que tem um papel importante na manutenção da taxa global de tradução, esta interação é enfraquecida na ausência de RNAs. A deficiência de DUSP3 também teria um impacto na interação das proteínas HNRNPC1/C2 e P53 in vitro. A ausência de DUSP3 diminui a interação HNRNPC-P53 através da hiperfosforilação da proteina HNRNPC1/C2. A perda desta interação, aumentaria os níveis da proteína P53 na célula deficiente de DUSP3 e poderia gerar parada no ciclo celular. Através de ensaios de imunofluorescência, se observo uma maior taxa de transcrição global na célula deficiente de DUSP3. Por fim, aqui demostramos que a interação direta de DUSP3 e HNRNPC1/C2 vai permitir a regulação das funções biológicas desta proteína, e a ausência de DUSP3 vai ter efeitos pleiotrópicos na homeostase da célula


inglêsProtein phosphorylation/dephosphorylation regulation is a central axis of many signaling cascades. DUSP3 phosphatase, consisting only of a single catalytic domain, plays key roles in cell proliferation and senescence. In HeLa cells subjected to genotoxic stress, DUSP3 physically interacts with HNRNPC proteins, but the effect of this molecular function is still unknown. Here we demonstrate that the absence of DUPS3 keeps the HNRNPC1/C2 proteins in a hyperphosphorylated state. To better understand the involvement of DUSP3- HNRNPC interaction on the biological functions of HNRNPC1/C2, DUSP3 deficient fibroblast cells were studied. The effect of DUSP3 deficiency on ribosome biogenesis was analyzed by polyribosome profile assay and RT-qPCR for rRNA quantification. The results showed that DUSP3 deficiency does not affect ribosomal subunit maturation, but would have an impact on transcription of pre-rRNAs and accumulation of 47S / 45S species. The expression of genes containing IRES sequences was analyzed by RT-qPCR and their translation throughout the cycle and under stress conditions. From expression, there is no difference in transcriptional levels of c-myc and xiap genes in normal and DUSP3 deficient cells under basal conditions. Although, the synthesis of these proteins is higher in deficient cells and these maintain a higher level of translation throughout the cell cycle. Under stress conditions, these two proteins always maintain higher expression in Knockdown cells for DUSP3. In this work, the presence of DUSP3 in the 40S ribosomal subunit complexes was also established by analyzing the fractions obtained from the polyribosome assay and in vitro interaction (CoIP). The presence of DUSP3 in the 40S subunits, 80S monosomes and polysomes could be through direct interaction with proteins that have an RRM domain and would be dependent on the complexes formed by the proteins and their target RNAs. Here we show the in vitro interaction of DUSP3 with PABP protein (with four RRM domains), a protein that plays an important role in maintaining the overall translation rate, this interaction is weakened in the absence of RNAs. DUSP3 deficiency would also have an impact on the interaction of HNRNPC1/C2 and P53 proteins in vitro. The absence of DUSP3 decreases HNRNPC-P53 interaction through hyperphosphorylation of the HNRNPC1/C2 proteins. Loss of this interaction would increase P53 protein levels in the DUSP3 deficient cell and could lead to cell cycle arrest. Through immunofluorescence assays, a higher overall transcription rate is observed in the DUSP3 deficient cell. Finally, we demonstrate that the direct interaction of DUSP3 and HNRNPC1/C2 will allow the regulation of the biological functions of this protein, and the absence of DUSP3 will have pleiotropic effects on cell homeostasis


Subject(s)
DNA Damage , Cell Cycle , Cells , Genes, myc , Origin of Life , Maintenance , Phosphorylation , Polyribosomes , Cell Cycle Checkpoints , Fibroblasts , Homeostasis
11.
São Paulo; s.n; s.n; 2020. 157 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1291880

ABSTRACT

A L-Asparaginase (L-ASNase) de Erwinia chrysathemi (ErA) é uma enzima amplamente utilizada para o tratamento da leucemia linfoblástica aguda (LLA). Embora o seu uso como segunda linha de tratamento para a LLA tenha proporcionado consideráveis benefícios clínicos, reações de hipersensibilidade e rápida depuração plasmática ainda são problemas recorrentes. Ademais, extensivos e custosos processos de produção da ErA são necessários para a obtenção da enzima pura. Com base nesses problemas, o presente trabalho propõe (1) o estudo de viabilidade de expressão da ErA em um sistema de síntese proteica livre de células (SPLC) e (2) a conjugação da proteína em bacteriófagos como ferramenta alternativa para o isolamento e monitoramento da depuração plasmática da ErA. Foram utilizados extratos celulares de Escherichia coli suplementados com solução energética contendo creatina fosfato (CP) como fonte de energia para síntese in vitro de ErA. Para conjugação da ErA a bacteriófagos, o sistema SpyTag/SpyCatcher foi implementado: SpyCatcher foi fusionado à porção N-terminal da ErA e bacteriófagos filamentosos da linhagem M13 e fd foram modificados de modo a expressar SpyTag nas proteínas de capsídeo pIII e pVIII, respectivamente. Em relação ao primeiro objetivo, o sistema de SPLC foi capaz de expressar a ErA com atividade. A proteína foi expressa na fração solúvel e apresentou atividade enzimática significativamente superior em relação à reação controle (7,07 ± 0,68 U/mL vs. 1,83 ± 0,14 U/mL). Tempo necessário para obtenção do extrato celular foi reduzido de 45 para 26 hrs, e sete componentes da solução energética foram removidos da composição original sem implicações negativas na eficiência de expressão da ErA, simplificando desta forma o processo de SPLC. Em relação ao segundo objetivo, ErA fusionada à SpyCatcher (SpyCatcher_ErA) foi conjugada com êxito em bacteriófagos capazes de expressar SpyTag fusionadas na porção N-terminal das proteínas pIII (SpyTag_pIII) e pVIII (SpyTag_pVIII). A porcentagem de formação dos conjugados entre SpyCatcher_ErA e SpyTag_pIII ((ErA)5-pIII) foi de 6% enquanto formação dos conjugados entre SpyCatcher_ErA e SpyTag_pVIII ((ErA)50-pVIII) foi de 46%, valores estes confirmados por atividade enzimática. Solução contendo conjugados foram injetados em camundongos e sequenciados/titulados com êxito. Não houve diferença de depuração plasmática entre (ErA)5-pIII e bacteriófago controle, mas houve maior taxa de eliminação de (ErA)50-pVIII em relação ao mesmo bacteriófago não conjugado à SpyCatcher_ErA. Os resultados aqui apresentados confirmam ser possível expressar ErA com atividade biológica em sistemas de SPLC. Além disso, o sistema de conjugação da ErA a bacteriófagos aqui desenvolvido foi capaz de monitorar a concentração de ErA presente na circulação em função do tempo, tornando-se uma potencial plataforma de desenvolvimento de novas proteoformas da ErA com características clínicas melhoradas


L-Asparaginase (L-ASNase) from Erwinia chrysanthemi (ErA) is a widely used enzyme for treatment of acute lymphoblastic leukemia (ALL). Although its use as a second-line treatment has provided significant clinical benefits, hypersensitivity reactions and a fast clearance rate are recurring L-ASNase-related problems. In addition, extensive and costly production processes are required for the manufacturing of pure ErA. Based on these drawbacks, this current work proposes (1) the study of the use of a cell-free protein synthesis (CFPS) system as a viable platform for the synthesis of ErA and (2) the conjugation of the protein on bacteriophages as an alternative tool for the isolation and monitoring of ErA clearance. Escherichia coli-derived cell extracts supplemented with a creatine phosphate-based energy solution were used to synthesize ErA in vitro. To conjugate ErA on bacteriophages, the SpyTag/SpyCatcher system was implemented: SpyCatcher was fused to the N-terminus of the ErA while filamentous phage strains M13 and fd were engineered in order to display SpyTag on their pIII and pVIII capsid proteins, respectively. Regarding the first goal, the CFPS system was able to express an active ErA. The protein was expressed in the soluble fraction and there presented a significant higher enzymatic activity compared to the control reaction (7.07 ± 0.68 U/mL vs. 1.83 ± 0.14 U/mL). Time required to obtain the cell extract was reduced from 45 to 26 hours, and seven energy solution reagents were removed from the original solution without compromising the efficiency of ErA expression, thus simplifying the CFPS process. With respect to the second goal, ErA fused to SpyCatcher (SpyCatcher_ErA) was sucessfully conjugated on bacteriophages capable of displaying SpyTag fused to the Nterminus of the pIII (SpyTag_pIII) or pVIII (SpyTag_pVIII) proteins. Percentage of conjugate formation between SpyCatcher_ErA and SpyTag_pIII (ErA)5-pIII was 6% whereas conjugate formation between SpyCatcher_ErA and SpyTag_pVIII (ErA)50-pVIII was 46%, values that were confirmed by enzymatic activity. Sample containing conjugates were injected into mice and sucessfully sequenced/titrated. No clearance differences were observed between (ErA)5- pIII and a control bacteriophage, but a higher clearance rate was observed for (ErA)50-pVIII compared to SpyTag_VIII non conjugated to SpyCatcher_ErA. The results here presented confirm the expression of a biologically active ErA from a CFPS system. Besides, the development of a conjugation system capable of linking ErA to bacteriophages could be used as a means to monitor the ErA concentration in the blood as a function of time and also as a potential platform to be used in the development of novel ErA proteoforms with improved clinical properties


Subject(s)
Asparaginase/analysis , Biological Products/adverse effects , In Vitro Techniques/methods , Efficiency , Enzymes , Erwinia/classification , Precursor Cell Lymphoblastic Leukemia-Lymphoma/classification , Cells , Dickeya chrysanthemi/classification , Monitoring , Capsid Proteins , Growth and Development , Escherichia coli/classification , Control/methods
12.
Braz. J. Pharm. Sci. (Online) ; 56: e18499, 2020. tab, graf
Article in English | LILACS | ID: biblio-1285512

ABSTRACT

Lignosus rhinocerotis (tiger milk mushroom) is widely used by the indigenous people of Malaysia as a traditional remedy. The present study was carried out in order to evaluate the antioxidant, cytotoxic and anti-neuroinflammatory activities of L. rhinocerotis extract on brain microglial cells (BV2). The antioxidant activity was evaluated by 2,2-diphenyl-1-picryhydrazyl (DPPH•), 2,2'-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS•+) scavenging assays, and ferric reducing antioxidant power (FRAP). The FRAP, DPPH and ABTS•+ scavenging capacities of the TE3 fraction were 420.77 mg FE/g, 58.01%, and 7%, respectively. The cytotoxic activity was determined by MTS assay. The in vitro model of anti-neuroinflammatory property was evaluated by measuring the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced BV2 cells. The TE3 fraction showed a significant NO reduction at 1 to 100 µg/mL. The TE3 fraction down-regulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) genes while it upregulated heme oxygenase (HO-1) and NADPH quinone acceptor oxidoreductase-1 (NQO-1) genes. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription was also activated. The chemical component of the active fraction (TE3) was identified by gas chromatography-mass spectrometry (GCMS). Overall, the BV2 in vitro model anti-neuroinflammatory activity of L. rhinocerotis may be caused by the lipid constituents identified in the fraction


Subject(s)
In Vitro Techniques/methods , Cells/classification , Agaricales/classification , Inflammation/drug therapy , Lipids/adverse effects , Gas Chromatography-Mass Spectrometry/instrumentation , Antioxidants/pharmacology
13.
São Paulo; s.n; s.n; 2019. 48 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-1049502

ABSTRACT

Biofármacos e produtos imunobiológicos representam uma parcela significativa no mercado farmacêutico global. Cerca de 400 milhões de pessoas em todo o mundo dependem desses produtos e, muitas vezes, necessitarão delas para o resto de suas vidas. Até o momento, a tecnologia convencional para síntese dessas proteínas recombinantes é a expressão baseada em células. Porém, este sistema está frequentemente associado a problemas como a degradação da proteína-alvo devido à presença de nucleases e proteases, agregação com formação de corpos de inclusão e perda de molde de DNA. A plataforma de síntese proteica livre de células (do inglês Cell-Free Protein Synthesis ou CFPS) tem surgido como uma alternativa à expressão baseada em célula, permitindo a síntese de diversas proteínas, inclusive as de difícil expressão, na forma solúvel, em elevado rendimento e com capacidade de escalonamento. Este estudo buscou sintetizar a proteína interferon-ß1b humano recombinante (rhINF-ß1b) no sistema CFPS. Através de um trabalho de bioinformática, otimizou-se a sequência nucleotídica da proteína para expressão em lisado de E. coli e construiu-se um vetor de expressão linear, contendo promotor T7, RBS, região codificadora e um terminador T7. O sistema CFPS aceita molde de DNA no formato linear, que possui a vantagem de agilidade na preparação, sem a necessidade das etapas de clonagem, transformação, cultivo, extração e purificação do DNA. Também foi testado a expressão em DNA plasmidial, em que o gene do IFN foi clonado em vetor TOPO-TA Cloning. Para comparar os níveis de expressão foi utilizado esses mesmos vetores no sistema baseado em célula, com cepas de BL21(DE3) e Rosetta(DE3). Apesar da proteína de interesse não ter sido sintetizada com sucesso no sistema CFPS, foram dados alguns passos importantes para atingir este objetivo. No futuro, uma das prioridades é padronizar um sistema livre de células do laboratório capaz de fornecer um elevado rendimento para síntese de proteínas


Biopharmaceutical and immunobiological products represent a growing share of the global pharmaceutical market. Around 400 million people worldwide are dependent of such proteins and, often, they are going to need for the rest of their lives. So far, the most employed biopharmaceutical production technology is cell-based expression. However, this system is usually associated with problems such as degradation of proteins due to the presence of endogenous nucleases or proteases, aggregation with inclusion bodies formation and loss of DNA template. Cell-Free Protein Synthesis (CFPS) platform has emerged as an alternative to cell-based expression, allowing synthesis of many types of proteins, including difficult-to-express proteins, proteins in soluble form, in high yield and possibility to scale up or down the process. This work sought to synthesize recombinant human interferon-ß1b (rhINF-ß1b) in CFPS system. Through a bioinformatics study, a nucleotide sequence of the target protein was optimized for expression in E. coli lysate and a linear DNA template was designed, containing a T7 promoter, a RBS, a coding sequence and a T7 terminator. The CFPS system accepts linear template DNA, which has the advantage of agility in the preparation, without the need for the steps of cloning, transformation, cultivation, extraction and purification of DNA template. Expression in plasmid DNA was also tested, wherein the IFN gene was cloned into TOPO-TA Cloning vector. To compare expression levels, the same vectors were used in the cell-based system with BL21 (DE3) and Rosetta (DE3) strains. Although the protein of interest was not successfully synthesized in the CFPS system, some important steps were taken to achieve this goal. In the future, one of the priorities is to standardize the lysate preparation for a high throughput protein production


Subject(s)
Recombinant Proteins/analysis , Computational Biology/instrumentation , Interferon beta-1b/analysis , Cells , Escherichia coli
14.
S. Afr. med. j. (Online) ; 109(8): 18-24, 2019. ilus
Article in English | AIM, AIM | ID: biblio-1271224

ABSTRACT

Background. The publicity around stem cell therapy has given many persons who have sustained a devastating injury such as spinal cord injury (SCI) the hope of achieving partial or full recovery from their injuries. Several phase I and II clinical trials are being conducted owing to positive results obtained in animal models. While safety during the trials has been demonstrated, clinical efficacy in the outcome of ethically approved trials is still lacking. Many persons affected by SCI are, however, desperate for a cure and are lured into undergoing stem cell therapy by marketing campaigns and information readily available on the internet. These people travel far and wide to undergo stem cell therapy, which has led to the term 'stem cell tourism'. Objectives. To compare the data from participants' self-report questionnaires before and after their stem cell therapy to determine if there were differences in their functional and neurological status, and to record details of the procedures. Method. Persons who sustained a SCI and who received apparent stem cell therapy in South Africa (SA) or elsewhere were recruited to participate in the present study. Volunteers who gave written informed consent were asked to complete a biographical questionnaire and validated self-report questionnaire (Spinal Cord Independence Measure version III (SCIM III)) before and after their stem cell therapy to determine if there were differences in their functional and neurological status. The results of the self-report questionnaires were compared with the published expected functional outcome of people with lesions at a similar level of SCI to the participants. The secondary aims of the study were to document details of the procedures and their locations, the sources of 'stem cells' and the cost. Results. There was no indication that the participants' functional outcomes, as measured by the self-reported SCIM III, were better than the expected level of functional ability in patients with similar injury levels. Likewise, the neurological motor recovery scored on the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) motor scores showed no improvement post stem cell therapy. Conclusion. This study highlights the need to curb the practice of offering unethical and non-evidence-based stem cell therapy for SCI. Ethical research and treatment is encouraged as well as an effective legal framework and education of health professionals, patients and their family members and caregivers, which will avoid unrealistic expectations, bogus therapies and the potential adverse effects of non-evidence-based 'stem cell therapies' offered by clinics via the internet


Subject(s)
Cells , Mesenchymal Stem Cells , South Africa , Spinal Cord Injuries
15.
S. Afr. med. j. (Online) ; 109(8): 25-29, 2019. ilus
Article in English | AIM, AIM | ID: biblio-1271225

ABSTRACT

Cellular therapy has become a billion-dollar industry and is set to become one of the therapeutic pillars of healthcare in the 21st century. Adult stem cells, which include haematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal/stem cells (MSCs), is one of the major cell types currently under investigation for use in cell therapy. This review focuses on HSPCs and MSCs and discusses their heterogeneous nature and the problems faced in expanding these cells to therapeutic numbers for use in clinical applications


Subject(s)
Cells , Gene Products, gag , Genetic Heterogeneity , Therapeutics
16.
S. Afr. med. j. (Online) ; 109(8): 59-64, 2019. ilus
Article in English | AIM, AIM | ID: biblio-1271231

ABSTRACT

tem cells have an inherent capacity to facilitate regeneration; this has led to unprecedented growth in their experimental use in various clinical settings, particularly in patients with diseases with few alternative treatment options. However, their approved clinical use has to date been restricted largely to haematological diseases and epidermal transplantation to treat severe burns. After thorough searching of two databases, this review illuminates the role of stem cell therapy for treatment of musculoskeletal diseases. Research suggests that successful application of stem cells as regenerative mediators is in all likelihood dependent on the ability of endogenous tissue-resident reparative mediators to respond to paracrine signals provided by the applied stem cells. Therefore, an understanding of how the pathological environment influences this process is crucial for the ultimate success of stem cell therapies. The current review presents both the progress and limitations of stem cells as regenerative mediators in the context of musculoskeletal disorders


Subject(s)
Cells , Musculoskeletal Physiological Phenomena , Regenerative Medicine , South Africa
17.
Chinese Journal of Biotechnology ; (12): 1942-1954, 2019.
Article in Chinese | WPRIM | ID: wpr-771741

ABSTRACT

The chemical manufacturing industry that uses fossil resources as raw materials, consumes non-renewable resources and also causes damage to the ecological environment, stimulating the development of bio-manufacturing with renewable resources as raw materials. Unlike traditional chemical manufacturing, bio-manufacturing uses cells as a "production workshop", and each process in the "workshop" is catalyzed by enzymes. In addition to mild reaction conditions, the "cell factory" has strong plasticity, and can be used to synthesize various target chemicals according to demand adjustment or reconstitution of metabolic pathways. The design process of the "cell factory" follows the following guidelines: 1) Construct an optimal synthetic route from raw materials to products; 2) Balance the metabolic flux of each reaction in the metabolic pathway, so that the metabolic flux of this pathway is much higher than the primary metabolism of the cells; 3) Precursor supply in the pathway should be sufficient, and adjust multiple precursors supply ratio as needed; 4) enzymatic reactions often involve the participation of various cofactors, smooth metabolic pathways need to balance or regenerate various cofactors; 5) Through genetic modification or process improvement to remove metabolic intermediates and products feedback inhibition to achieve higher yields.


Subject(s)
Biotechnology , Cells , Metabolism , Coenzymes , Metabolism , Metabolic Engineering , Metabolic Networks and Pathways , Genetics
18.
São Paulo; IAL; 2019. 15 p. ilus, graf, tab.
Non-conventional in Portuguese | SES-SP, LILACS, SES-SP, SESSP-IALPROD, SES-SP | ID: biblio-1007411

ABSTRACT

Leishmaniasis is a neglected disease that affects more than 12 million people, with a limited therapy. plant-derived natural products represent a useful source of anti-protozoan prototypes. In this work, four derivatives were prepared from neolignans isolated from the Brazilian plant Nectandra leucantha, and their effects against intracellular amastigotes of Leishmania (L.) infantum evaluated in vitro. IC50 values between 6 and 35 µM were observed and in silico predictions suggested good oral bioavailability, no pAINs similarities, and ADMet risks typical of lipophilic compounds. the most selective (sI > 32) compound was chosen for lethal action and immunomodulatory studies. this compound caused a transient depolarization of the plasma membrane potential and induced an imbalance of intracellular Ca2+, possibly resulting in a mitochondrial impairment and leading to a strong depolarization of the membrane potential and decrease of ATP levels. The derivative also interfered with the cell cycle of Leishmania, inducing a programmed cell death-like mechanism and affecting DNA replication. Further immunomodulatory studies demonstrated that the compound eliminates amastigotes via an independent activation of the host cell, with decrease levels of IL-10, TNF and MCP-1. Additionally, this derivative caused no hemolytic effects in murine erythrocytes and could be considered promising for future lead studies.


Subject(s)
Cells , Disease , Leishmania
19.
Coluna/Columna ; 17(3): 237-239, July-Sept. 2018.
Article in English | LILACS | ID: biblio-952933

ABSTRACT

ABSTRACT The intervertebral disc (IVD) is one of the parts of the body most commonly affected by disease, and it is only recently that we have come closer to understanding the reasons for its degeneration, in which nutrient supply plays a crucial role. In this literature review, we discuss the basic principles and characteristics of energy supply and demand to the IVD. Specifically, we review how different metabolites influence IVD cell activity, the effects of mechanical loading on IVD cell metabolism, and differences in energy metabolism of the annulus fibrous and nucleus pulposus cell phenotypes. Determining the factors that influence nutrient supply and demand in the IVD will enhance our understanding of the IVD pathology, and help to elucidate new therapeutic targets for IVD degeneration treatment.


RESUMO O disco intervertebral (IVD) é uma das partes mais comuns do corpo e apenas recentemente nos aproximamos de compreender as razões da sua degeneração, em que o suprimento de nutrientes desempenha um papel crucial. Nesta revisão da literatura, discutimos os princípios básicos e as nuances do fornecimento e da demanda de energia para o IVD. Específicamente, analisamos como os diferentes metabólitos influenciam na atividade das células IVD, os efeitos da carga mecânica no metabolismo das células IVD, a diferença no metabolismo energético dos fenótipos das células fibrosas e do núcleo do pulposus anelar. A determinação de fatores que influenciam o suprimento e a demanda de nutrientes no IVD aumentará nossa compreensão da patologia IVD e ajudará a elucidar novos alvos terapêuticos para o tratamento da degeneração IVD.


RESUMEN El disco intervertebral (IVD, por sus siglas en inglés) es una de las partes más comúnmente enfermas del cuerpo y solo recientemente nos acercamos a la comprensión de los motivos de su degeneración, de los cuales el suministro de nutrientes juega un papel crucial. En esta revisión de la literatura discutimos los principios básicos y los matices de la oferta y demanda de energía para el IVD. Específicamente, revisamos cómo los diferentes metabolitos influyen en la actividad de las células IVD, los efectos de la carga mecánica sobre el metabolismo de las células IVD y las diferencias en el metabolismo energético de los fenotipos de las células del anillo fibroso y el núcleo pulposo. La determinación de los factores que influyen en la oferta y demanda de nutrientes en el IVD mejorará nuestra comprensión de la patología IVD y ayudará a dilucidar nuevos objetivos terapéuticos para el tratamiento de la degeneración IVD.


Subject(s)
Humans , Intervertebral Disc/pathology , Cells/metabolism , Energy Metabolism , Intervertebral Disc/anatomy & histology , Intervertebral Disc/abnormalities
20.
MedUNAB ; 20(3): 319-326, 2018.
Article in Spanish | LILACS | ID: biblio-965042

ABSTRACT

Introducción: La bibliometría mide variables de la literatura científica que se describen de forma cuantitativa por medio de análisis estadístico; con esta herramienta se busca evidenciar el impacto de los trasplantes de células madre hematopoyéticas en la literatura de los últimos 45 años. Objetivo: Descripción de la literatura médica indexada en MEDLINE desde 1970 hasta 2015 sobre trasplantes de células madre hematopoyéticas. Metodología: Se realizó una búsqueda en la base de datos MEDLINE a través de GoPubMed y Fabumed. La estrategia de búsqueda fue: "Hematopoietic Stem Cell Transplantation" [Majr] AND "1970:2015"[dp]. Las variables analizadas fueron el número de publicaciones por año, revistas, países y porcentaje de publicaciones sobre trasplantes de células madre hematopoyéticas. Resultados: Se recuperaron 23,295 referencias sobre trasplantes de células madre hematopoyéticas. Se identificaron 1,844 revistas diferentes, el mayor número de publicaciones se encontró en Bone Marrow Transplantation con 2,443 publicaciones, seguida de Blood con 1,375 y Biology of Bone Marrow Transplantation con 1,319 referencias. Estados Unidos fue el país con mayor número de publicaciones con 7,491 (32.15%); en Latinoamérica fueron publicados 324 (1.39%). Los descriptores de la literatura más investigados relacionados con el tema fueron: Trasplante de células madre hematopoyéticas con 23,345 publicaciones, humanos con 22,019 y células madre con 17,564. Conclusiones: Las publicaciones sobre trasplantes de células madre hematopoyéticas han incrementado de forma progresiva durante los 45 años estudiados. Los países desarrollados son los que han realizado mayor investigación del tema, en contraste con el número de publicaciones en total. [Ríos-Moreno JV, Bueno-Flórez SJ, Conde-Hurtado DI, Tarazona N, Sossa-Melo Claudia Lucía. Estudio bibliométrico: 45 años de literatura biomédica en trasplante de células madre hematopoyéticas. MedUNAB 2017-2018; 20(3): 319-326].


Introduction: Bibliometric measures variables from the scientific literature that are described quantitatively by means of statistical analysis; this tool seeks to demonstrate the impact of hematopoietic stem cell transplants in the literature throughout the last 45 years. Objective: To describe the indexed medical literature in MEDLINE from 1970 to 2015 on hematopoietic stem cell transplants. Methodology: A search of the MEDLINE database through GoPubMed and Fabumed was performed. The search strategy was: Hematopoietic Stem Cell Transplantation [Majr] and 1970:2015 [dp]. The variables analyzed were the number of publications per year, journals, countries and percentage of publications on hematopoietic stem cell transplants. Results: 23,295 references were recovered on hematopoietic stem cell transplants. 1,844 different journals were identified, the largest number of publications was found in Bone Marrow Transplantation with 2,443 publications, followed by Blood with 1,375 and Biology of Bone Marrow Transplantation with 1,319 references. The United States was the country with the highest number of publications with 7,491 (32.15%), in Latin America 324 (1.39%) were published. The most researched descriptors of literature related to the topic were: Transplantation of hematopoietic stem cells with 23,345 publications, humans with 22,019 and stem cells with 17,564. Conclusions: The publications on hematopoietic stem cell transplants have increased progressively during the 45 years studied. The developed countries are the ones that have done more research on the subject, in contrast to the number of publications in total. [Ríos-Moreno JV, Bueno-Flórez SJ, Conde-Hurtado DI, Tarazona N, Sossa-Melo Claudia Lucía. A Bibliometric Study: 45 Years of Biomedical Literature in Hematopoietic Stem Cell Transplantation. MedUNAB 2017-2018; 20(3): 319-326].


Introdução: A bibliometria mede variáveis da literatura científica que são descritas quantitativamente por meio de análise estatística; esta ferramenta procura demonstrar o impacto dos transplantes de células estaminais hematopoiéticas na literatura dos últimos 45 anos. Objetivo: Descrição da literatura médica indexada em MEDLINE de 1970 a 2015 em transplantes de células-tronco hematopoiéticas. Metodologia: uma pesquisa do banco de dados MEDLINE foi realizada através do GoPubMed e Fabumed. Aestratégia de busca foi: "Transplante de células estaminais hematopoiéticas" [Majr] AND "1970: 2015" [dp]. As variáveis analisadas foram o número de publicações por ano, periódicos, países e porcentagem de publicações sobre transplantes de células estaminais hematopoiéticas. Resultados: Foram recuperadas 23,295 referências, em transplantes de células estaminais hematopoiéticas. Identificamos 1,844 periódicos diferentes; o maior número de publicações foi encontrado no Transplante de medula óssea com 2,443 publicações, seguido de sangue com 1,375 e Biologia do transplante de medula óssea com 1,319 referências. Os Estados Unidos foi o país com maior número de publicações com 7,491 (32.15%); na América Latina, foram publicados 324 (1.39%). Os textos mais pesquisados da literatura relacionados com o tema foram: Transplante de células-tronco hematopoiéticas com 23,345 publicações, humanos com 22,019 e células-tronco com 17,564. Conclusões: As publicações sobre transplantes de células estaminais hematopoiéticas aumentaram progressivamente durante os 45 anos estudados. Os países desenvolvidos são os que fizeram mais pesquisas sobre o assunto, em contraste com o número de publicações no total. [Ríos-Moreno JV, Bueno-Flórez SJ, Conde-Hurtado DI, Tarazona N, Sossa-Melo Claudia Lucía. Estudo bibliométrico: 45 anos de literatura biomédica em transplante de células-tronco hematopoiéticas. MedUNAB 2017-2018; 20(3): 319-326].


Subject(s)
Stem Cells , Hematopoietic Stem Cell Transplantation , Bibliometrics , Cells , MEDLINE , Bone Marrow Transplantation , Review , Cell Transplantation , Hematology
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