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1.
Braz. j. biol ; 832023.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469147

RESUMO

Abstract The -lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p 0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.


Resumo Os medicamentos combinados de -lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.

2.
Braz. j. biol ; 83: e239323, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1339341

RESUMO

Abstract The β-lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p<0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.


Resumo Os medicamentos combinados de β-lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p < 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.


Assuntos
Humanos , Infecções por Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/epidemiologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Escherichia coli , Bactérias Gram-Negativas
3.
Clin Transl Oncol ; 24(7): 1403-1412, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35133601

RESUMO

PURPOSE: The role of autophagy in prostate cancer metastasis remains controversial, and the effects of the autophagy-related gene ATG5 on prostate cancer metastasis are poorly understood. This study aims to explore the effects of ATG5 on prostate cancer metastasis and its molecular mechanism. METHODS: The metastatic characteristics of LNCaP and DU145 cells were assessed by NOD/SCID mouse experiments, western blot, transwell assay, and wound-healing assay. Double membrane autophagic vesicle observation and the adenovirus-expressing mCherry-GFP-LC3B fusion protein were used to assess the autophagic characteristics of LNCaP and DU145 cells. The role of p62 in the accumulation of TWIST1 was confirmed by western blot under different conditions. The lentivirus particles of shATG5, NOD/SCID mice experiments, western blot, transwell assay, and wound-healing assay were used to confirm the role of ATG5 in TWIST1 accumulation and prostate cancer cell metastasis. RESULTS: We identified a stabilizing effect of p62 on TWIST1 in the autophagic regulation of EMT and prostate cancer metastasis. The loss of ATG5 in DU145 cells resulted in autophagy deficiency and p62 accumulation, which stabilized TWIST1 and increased the TWIST1 level in prostate cancer cells, and eventually promoted EMT and metastasis. In comparison, LNCaP cells with regular ATG5 expression and autophagy status retained remarkable epithelial cell characteristics and had limited metastatic characteristics. Similar results were also found in wild-type LNCaP cells and LNCaP cells with stable ATG5 interference. CONCLUSIONS: Our research revealed ATG5-mediated autophagy as a key mechanism that controls the metastasis of prostate cancer by regulating p62 abundance and TWIST1 stabilization.


Assuntos
Neoplasias Pulmonares , Neoplasias da Próstata , Animais , Autofagia , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas Nucleares , Neoplasias da Próstata/patologia , Proteína 1 Relacionada a Twist
4.
Braz J Biol ; 83: e239323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34524371

RESUMO

The ß-lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p<0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.


Assuntos
Antibacterianos , Infecções por Bactérias Gram-Negativas , Antibacterianos/uso terapêutico , Escherichia coli , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
5.
Braz. j. biol ; Braz. j. biol;81(3): 526-536, July-Sept. 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1153404

RESUMO

Abstract To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.


Resumo Investigar a concentração ideal de andrógenos em cultura de folículos pilosos de carneiro Hetiano e detectar os efeitos da concentração de andrógenos na proliferação e apoptose de células foliculares, por meio de imunofluorescência e de determinação quantitativa, em tempo real, da fluorescência dos níveis de expressão gênica de proteína associada à queratina. Folículos pilosos foram isolados por microdissecção, e folículos de lã e pedaços de pele foram cultivados em várias concentrações de di-hidrotestosterona (DHT) em meio de cultura. Em seguida, medições diárias de crescimento longitudinal dos folículos capilares foram obtidas usando um micrômetro microscópico. Folículos de lã cultivados de Hetianos foram corados pelo método SACPIC para revelar a estrutura do folículo piloso, enquanto fatias de pele de carneiro foram usadas para observar a proliferação celular por imunocoloração e apoptose celular por meio do método TUNEL. Em âmbito da biologia molecular, a expressão gênica da proteína associada à queratina (Kap) foi estudada usando folículos capilares cultivados por vários dias, in vitro. Os efeitos das concentrações de andrógenos no crescimento e desenvolvimento dos folículos de lã de Hetianos foram estudados experimentalmente. Ensaios de proliferação de EdU revelaram que o andrógeno promoveu a proliferação celular dentro das papilas dérmicas do folículo piloso. A detecção de apoptose por TUNEL demonstrou que o tratamento com andrógeno poderia atrasar a apoptose celular. Os resultados da reação em cadeia da polimerase transcrição reversa quantitativa (qPCR) demonstraram que os padrões de expressão gênica da proteína de enxofre Kap1.1, KIF1.2, Kap2.12 e Kap4.2 foram significativamente maiores no grupo de ovinos Hetianos de montanha. Uma concentração de androgênio de 100 nM pode promover o crescimento de células foliculares de lã de Hetianos in vitro, resultando na superexpressão de alguns genes da família Kap.


Assuntos
Animais , , Queratinas/genética , Ovinos , Folículo Piloso , Androgênios/farmacologia
6.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(3): 536-542, 2021 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-34145857

RESUMO

OBJECTIVE: To analyze the recent severity of COVID-19 in various countries. METHODS: Data were ollected on the epidemic situation of COVID-19 in various countries as of January 16, 2021, and the scale and overall trend of the epidemic were retrospectively described; combined with the recent trend of newly confirmed cases, from January 10 to 16 (the 54th week) and the newly confirmed cases indexes, such as the number and incidence density the severity of the epidemic was classified. Feasible suggestions were put forward based on the variation of the virus, actual data of vaccine research and development and possible existence in many countries. RESULTS: Up to January 16, 2021, there were 92 510 419 confirmed cases worldwide; 4 849 301 new confirmed cases were confirmed in the 54th week, and they were still growing. Among all the continents, the cumulative number of confirmed cases in Europe, North America, and Asia has exceeded 21 million, and the number of new confirmed cases in a single week in North America, South America and Asia were all increasing. Among the countries, the cumulative number of confirmed cases in 18 countries including the United States, India, and Brazil was more than 1 million, accounting for 77.04% of the total number of cumulative confirmed cases in the world. Eleven countries including the United States, Brazil, France, Spain, Colombia, The United Kingdom, Russia, Germany, South Africa, Italy, and India are at higher risk of the epidemic; The United States, Brazil, France, Spain, and Colombia were still experiencing new confirmed cases and increasing status, the risk of the epidemic was greater. Novel coronavirus mutates frequently, up to February 2021, there had been 3 931 mutant genotypes in the world. At the same time, a total of 11 vaccines were successfully launched, however we were still facing some troubles, such as the global shortage of vaccines, the public's willingness to vaccinate needed to be improved, and equity in the distribution of vaccines. CONCLUSION: The global epidemic situation is still getting worse, with repeated epidemics in all the continents and countries, and has not been fundamentally controlled. At the continent level, North America, South America, and Europe have the most severe epidemics; at the national level, The United States, Brazil, France, Spain, Colombia and other countries have higher epidemic risks. Focusing on the severely affected countries will help bring the global epidemic under control as soon as possible. Under the premise of ensuring the safety and effectiveness of the vaccines, it is a key and feasible direction to improve the yield and vaccination rate of the vaccines, shorten the onset time of the vaccines and prolong the immune persistence.


Assuntos
COVID-19 , Ásia , Brasil , Europa (Continente) , França , Humanos , Índia , Itália , América do Norte , Estudos Retrospectivos , SARS-CoV-2 , Espanha , Reino Unido , Estados Unidos
7.
Clin Transl Oncol ; 23(9): 1769-1781, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33689097

RESUMO

BACKGROUND: The development and progression of colon cancer are significantly affected by the tumor microenvironment, which has attracted much attention. The goal of our study was primarily to find out all possible tumor microenvironment-related genes in colon cancer. METHOD: This study quantified the immune and stromal landscape using the ESTIMATION algorithm using the gene expression matrix obtained from the UCSC Xena database. Dysregulated genes were harvested using the limma R package, and relevant pathways and biofunctions were identified using enrichment analysis. A least absolute shrinkage and selection operator (LASSO) regression was used to select the pivotal genes from the DEGs. Then, survival analysis was performed to determine the hub genes and a prognostic model was constructed by these hub genes with (or) TNM stage. Besides, associations between hub gene expressions and immune cell infiltration were assessed. RESULTS: A total of 725 DEGs were identified. Most of the results of the enrichment analysis were immune-related items. 13 genes were selected as the hub genes and a moderate-to-strong positive correlation between most hub genes and several immune cells were observed. Besides, the prognostic value of the hub genes were comparable to TNM staging. CONCLUSIONS: Our study provides a better understanding of how interactions between the 13 immune-prognostic hub genes and immune cells in the tumor microenvironment affect biological processes in colon cancer. These genes exhibit an equivalent ability to TNM staging in prognosis prediction. They are particularly expected to become novel prognostic biomarkers and targets of immunotherapies for colon cancer.


Assuntos
Algoritmos , Neoplasias do Colo/genética , Expressão Gênica , Microambiente Tumoral/genética , Fatores Etários , Idoso , Neoplasias do Colo/mortalidade , Neoplasias do Colo/fisiopatologia , Bases de Dados Genéticas , Feminino , Marcadores Genéticos/genética , Humanos , Imunidade Celular , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Transcriptoma , Microambiente Tumoral/imunologia
8.
Braz J Biol ; 81(3): 526-536, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33470295

RESUMO

To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.


Assuntos
Queratinas , , Androgênios/farmacologia , Animais , Folículo Piloso , Queratinas/genética , Ovinos
9.
Clin Transl Oncol ; 23(4): 902-910, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32939659

RESUMO

BACKGROUND: Chemoresistance is the major cause of therapeutic failure in triple negative breast cancer (TNBC). In this work, we investigated the molecular mechanism for the development of TNBC chemoresistance. METHODS: mRNA and protein levels of ST8SIA1 were analyzed in chemosensitive and chemoresistant TNBC cells and tissues. Proliferation and survival assays were performed to determine the role of ST8SIA1 in TNBC chemoresistance. RESULTS: We found that ST8SIA1 mRNA and protein levels were increased in multiple TNBC cell lines after prolonged exposure to chemotherapeutic drugs. Consistently, retrospective study demonstrated that the majority of TNBC patients who developed chemoresistance displayed upregulation of ST8SIA1. We further found that chemoresistant TNBC cells were more sensitive than chemosensitive cells to ST8SIA1 inhibition in decreasing growth and viability. Consistently, ST8SIA1 inhibition augmented the efficacy of chemotherapy in TNBC cells. Mechanism studies demonstrated that ST8SIA1 inhibition led to suppression of FAK/Akt/mTOR and Wnt/ß-catenin signalling pathways. CONCLUSIONS: These findings provide an explanation for the heterogeneity of chemotherapy responses across TNBC individuals and reveal the supportive roles of ST8SIA1in TNBC chemoresistance.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Sialiltransferases/antagonistas & inibidores , Serina-Treonina Quinases TOR , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Via de Sinalização Wnt , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , N-Acetilgalactosaminiltransferases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Estudos Retrospectivos , Sialiltransferases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima
10.
Braz. J. Biol. ; 81(3): 526-536, jul. set. 2021. ^ilus, tab, graf
Artigo em Inglês | VETINDEX | ID: vti-31427

RESUMO

To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.(AU)


Investigar a concentração ideal de andrógenos em cultura de folículos pilosos de carneiro Hetiano e detectar os efeitos da concentração de andrógenos na proliferação e apoptose de células foliculares, por meio de imunofluorescência e de determinação quantitativa, em tempo real, da fluorescência dos níveis de expressão gênica de proteína associada à queratina. Folículos pilosos foram isolados por microdissecção, e folículos de lã e pedaços de pele foram cultivados em várias concentrações de di-hidrotestosterona (DHT) em meio de cultura. Em seguida, medições diárias de crescimento longitudinal dos folículos capilares foram obtidas usando um micrômetro microscópico. Folículos de lã cultivados de Hetianos foram corados pelo método SACPIC para revelar a estrutura do folículo piloso, enquanto fatias de pele de carneiro foram usadas para observar a proliferação celular por imunocoloração e apoptose celular por meio do método TUNEL. Em âmbito da biologia molecular, a expressão gênica da proteína associada à queratina (Kap) foi estudada usando folículos capilares cultivados por vários dias, in vitro. Os efeitos das concentrações de andrógenos no crescimento e desenvolvimento dos folículos de lã de Hetianos foram estudados experimentalmente. Ensaios de proliferação de EdU revelaram que o andrógeno promoveu a proliferação celular dentro das papilas dérmicas do folículo piloso. A detecção de apoptose por TUNEL demonstrou que o tratamento com andrógeno poderia atrasar a apoptose celular. Os resultados da reação em cadeia da polimerase transcrição reversa quantitativa (qPCR) demonstraram que os padrões de expressão gênica da proteína de enxofre Kap1.1, KIF1.2, Kap2.12 e Kap4.2 foram significativamente maiores no grupo de ovinos Hetianos de montanha. Uma concentração de androgênio de 100 nM pode promover o crescimento de células foliculares de lã de Hetianos in vitro, resultando na superexpressão de alguns genes da família Kap.(AU)


Assuntos
Animais , Ovinos , Androgênios/efeitos adversos , Androgênios/análise , Queratinas/análise
11.
Clin Transl Oncol ; 22(10): 1762-1777, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32239427

RESUMO

PURPOSE: Long non-coding RNAs (lncRNAs) have participated in progression of colorectal cancer. This study aims to study the role of RUNX1/RNCR3/miR-1301-3p/AKT1 axis in colorectal cancer. METHODS: The cancer tissues were from patients with colorectal cancer. The qRT-PCR was used to determine expression of lncRNA RNCR3, miR-1301-3p, and AKT1. Both dual-luciferase reporter assay and ChIP assay were conducted to investigate the binding sites of RUNX1 on RNCR3 promoter. Western blot was performed to analyze expression of AKT1 protein. Both dual-luciferase reporter assay and RIP assay were performed to detect the interacting sites between RNCR3 and miR-1301-3p. The CCK-8 assay, soft agar assay, transwell assay, and annexin-V-FITC/PI staining were applied to analyze the cell growth, invasion, and apoptosis, respectively. RESULTS: The data demonstrated that RNCR3 was elevated in colorectal cancer, and it was negatively correlated with expression of miR-1301-3p which was decreased in cancers. Then, RNCR3 could interact with and suppress miR-1301-3p expression in HCT116 and SW480. Knockdown of RNCR3 or miR-1301-3p overexpression significantly inhibited cell growth, invasion, and increased apoptosis through suppressing expression of Cyclin A1, PCNA, N-cadherin, Bcl-2, and promoting expression of E-cadherin, Bax in vitro and in vivo. RUNX1 was directly bound to RNCR3 promoter to activate RNCR3 expression. Furthermore, overexpression of RNCR3 blocked tumor inhibitory effects of miR-1301-3p on proliferation, colony formation, invasion, and apoptosis in vitro and in vivo. Additionally, RNCR3 and miR-1301-3p synergistically modulated AKT1 expression. CONCLUSION: RUNX1-activated upregulation of RNCR3 promoted colorectal cancer progression by sponging miR-1301-3p to elevate AKT1 levels in vitro and in vivo.


Assuntos
Apoptose , Neoplasias Colorretais/patologia , Subunidade alfa 2 de Fator de Ligação ao Core/fisiologia , MicroRNAs/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , RNA Longo não Codificante/fisiologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Regulação para Cima
12.
Clin Transl Oncol ; 22(10): 1741-1749, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32052381

RESUMO

OBJECTIVE: To observe the effects of different doses of propofol on the growth of transplanted liver tumor in BALB/C mice and check the expression of PCNA, CD34 and pAKT proteins to clarify the mechanism on molecule level. METHOD: Human primary liver cancer cells SMMC-7721 were subcutaneously cultured in BALB/C mice, and the transplanted tumor model of BALB/C mice was constructed. Forty mice successfully modeled were randomly divided into 5 groups (n = 8): the blank control group (group C), low-fat milk group (group I), low-dose (50 mg/kg) propofol group (P1), middle-dose (100 mg/kg) propofol group (P2) and high dose (150 mg/kg) propofol group (P3). Tumor volume changes were observed at 3, 6, 9, 12, 15 and 18 days (T1, T2, T3, T4, T5, T6 and T7) before and after administration of the drug, and tumor growth curves were plotted. After 19 days of administration, all mice were killed for tumor collection, tumor weight was measured, and the tumor inhibition rate of propofol was calculated. The protein expression of cluster of differentiation 34 (CD34) in transplanted tumor was detected by immunohistochemistry, and the protein expression of proliferating cell nuclear antigen (PCNA) and phospho-Akt (pAKT) was detected by immunofluorescence. RESULTS: Compared with group C, there was no significant difference in tumor volume in group I. At T2 ~ 7, the tumor volume of group P1, P2 and P3 decreased successively (P < 0.05). There was no significant difference in the inhibitory rate of tumor in group I, and the inhibitory rate of tumor in group P1, P2 and P3 increased successively (P < 0.05). There was no significant difference in PCNA, CD34, and pAKT protein expression in group I, while PCNA, CD34, and pAKT protein content in P1, P2, P3 groups were successively decreased (P < 0.05). CONCLUSION: Propofol had a dose-dependent effect on the growth of liver cancer xenografts in mice, inhibiting the expression of PCNA, CD34 and pAKT proteins, and the effect was most obvious in the 150 mg/kg propofol group.


Assuntos
Antígenos CD34/análise , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Antígeno Nuclear de Célula em Proliferação/análise , Propofol/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/análise , Animais , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Propofol/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
An Acad Bras Cienc ; 91(3): e20180424, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553364

RESUMO

Abstract: Cardiovascular diseases (CVDs) are leading causes of death in the world, owing to noticeable incidence and mortality. Traditional Chinese Medicine (TCM) SINI Decoction (SND) is used to prevent and treat CVDs, which has attracted extensive attention for its moderate and little side effects. However, the involved molecular mechanisms are exceedingly complicated and remain unclear. Systems pharmacology, as a novel approach that integrates systems biology and pharmacology plays a significant role in investigating the molecular mechanism of TCM. In systems pharmacology approach, we use to systematically uncover the mechanisms of action in Chinese medicinal formula SND as an effective treatment for CVDs, which mainly includes:1) molecular database building; 2) ADME evaluation; 3) target-fishing 4) network construction and analysis. The results show that 78 underlying valid ingredients and their corresponding 71 direct targets of SND were obtained. And SND take part in cardiomyocyte protection, blood pressure regulation, and lipid regulation module in treatment of CVDs by cooperative way. Systems pharmacology as an emerging field that investigates the molecular mechanisms of TCM through pharmacokinetic evaluation target prediction, and pathway analysis, which will facilitate the development of traditional Chinese herbs in modern medicine.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Redes Neurais de Computação , Biologia de Sistemas/métodos , Humanos , Modelos Biológicos
14.
Rev. Soc. Cardiol. Estado de Säo Paulo ; 29(Suppl. 2b): 117-117, Jun. 2019.
Artigo em Português | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1009204

RESUMO

A varfarina é um anticoagulante utilizado na prevenção e no tratamento de doenças tromboembólicas, com janela terapêutica estreita e, elevado risco de hemorragias. Nos idosos, a principal indicação para tratamento anticoagulante oral é fibrilação atrial, cuja prevalência aumenta com a idade, atingindo 8% após os 80 anos. O exame utilizado para controle da anticoagulação oral é o tempo de protrombina, através do cálculo da razão normalizada internacional (RNI), visando o ajuste de dose e manutenção da faixa terapêutica (RNI= 2 a 3). Os idosos requerem um monitoramento efetivo devido a fatores inerentes da idade. Embora seja conhecido que os fatores genéticos influenciam na resposta terapêutica à varfarina, na rotina da maioria dos hospitais a farmacogenética ainda não é considerada no ajuste de dose. Visando estabelecer uma conduta terapêutica personalizada, o presente estudo tem como objetivo avaliar a associação entre o polimorfismo rs9934438 do gene VKORC1, que codifica a enzima vitamina K epóxido redutase, e a dose semanal de varfarina necessária para atingir o RNI adequado. Até o momento, foram incluídos 52 pacientes com idade superior a 70 anos, de ambos os sexos e em uso de varfarina. A análise do polimorfismofoi realizada através da PCR em tempo real utilizando os reagentes TaqMan™ Sample-to-SNP™ e o sistema de detecção TaqMan® SNP Genotyping Assay. As análises estatísticas foram realizadas utilizando o pacote SPSS v. 16.0 e nível de significância adotado foi de 5%. Dos 52 pacientes incluídos até o momento, 37 (71%) permaneceram na faixa terapêutica (Time in Therapeutic Range, TTR) em pelo menos 50% do tempo de anticoagulação e, para eles a dose semanal de varfarina variou de 15mg a 62,5mg. Apesar de ser um estudo piloto, a distribuição dos genótipos está em equilíbrio gênico, segundo Hardy-Weinberg (AA=19,2%, AG=34,6%, GG= 46,2%, χ2= 3,34 e p=0,067). Para os idosos com TTR ≥50%, a frequência do alelo A foi significantemente maior entre os pacientes que utilizaram doses menores de varfarina (Exato de Fisher, p=0,005). Adicionalmente, os portadores do genótipo AA necessitaram, em média, de aproximadamente metade da dose para atingir a faixa terapêutica quando comparados aos portadores do genótipo GG, 20,5 versus 36,5 mg/semana, respectivamente (ANOVA, p=0,006/ Pós-teste Bonferroni, p=0,039). Os resultados permitem concluir que portadores de alelo A são mais responsivos ao tratamento com varfarina, sugerindo que o perfil genotípico pode ser de grande valor para o direcionamento da dose terapêutica em idosos. (AU)


Assuntos
Humanos , Varfarina , Idoso
15.
Clin Transl Oncol ; 21(12): 1634-1643, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30911882

RESUMO

OBJECTIVE: To assess the effect of the intraoperative application of the Aquamantys® system to treat the hepatic resection margin on local and overall recurrence of HCC. METHODS: We retrospectively analyzed 101 patients admitted from November 2016 to June 2018 who underwent hepatectomy using the Aquamantys® as hemostatic device, who were matched with 101 patients (control group) using conventional hemostatic devices through PSM. Univariate and multivariate analyses of recurrence-free survival (RFS) and local recurrence-free survival (LRFS) were performed using the Cox proportional hazard model. RESULTS: There were no significant differences in baseline data and surgical procedures between the two groups. The Aquamantys® group showed less blood loss (P = 0.005) and a lower blood transfusion rate (P = 0.036), while the incidences of postoperative complications of the two groups showed no difference (P = 0.266). OS rates of the Aquamantys® group and the control group were 82.6% and 84.2%, respectively (P = 0. 446), and RFS rates were 65.5% and 58.2%, respectively (P = 0.153), with no significant differences. The Aquamantys® group and the control group had two cases and 11 cases of local recurrence, respectively, with LRFS rates of 98% and 87.9%, respectively, in the follow-up period, corresponding to a significant difference (P = 0.011). Multivariate analysis showed that microvascular invasion (MVI), tumor diameter > 5 cm, and the control group were independent risk factors for LRFS. CONCLUSION: Our results indicate that application of the Aquamantys® system in hepatectomy can reduce local recurrence, but it can neither reduce overall recurrence nor improve OS.


Assuntos
Carcinoma Hepatocelular/cirurgia , Eletrocirurgia/instrumentação , Hemostasia Cirúrgica/instrumentação , Hepatectomia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue/estatística & dados numéricos , Carcinoma Hepatocelular/prevenção & controle , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Hemostasia Cirúrgica/métodos , Humanos , Neoplasias Hepáticas/prevenção & controle , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Pontuação de Propensão , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos
16.
Clin Transl Oncol ; 21(9): 1186-1196, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30694461

RESUMO

BACKGROUND: Annexin family consist of 12 members, many of them are frequently dysregulated in human cancers. However, the diagnosis and prognosis of Annexin family expression in acute myeloid leukemia (AML) remain elusive. The aim of the present study was to assess the prognostic value of Annexin expressions in adult and pediatric AML. METHODS: GenomicScape tool was used to assess the prognostic value of the expressions of Annexin family members in a cohort of 162 adult AML patients. Quantitative reverse transcript real-time PCR (QRT-PCR) was performed to detect the ANXA2 expression level in the bone marrow-derived mononuclear cells (BMMCs) obtained from 101 pediatric AML patients and 30 controls. RESULTS: The results demonstrated that high mRNA expressions of ANXA2, ANXA6, and ANXA7 were significantly associated with worse prognosis, while ANXA5 was correlated with better prognosis in adult AML. QRT-PCR analysis showed that ANXA2 expression was dramatically downregulated in BMMCs of pediatric AML patients compared to controls (p < 0.0001). ROC analysis demonstrated that ANXA2 could efficiently differentiate pediatric AML patients from controls (AUC 0.872, p < 0.0001). Likewise, ANXA2 was significantly lower in AML patients with poor-risk karyotype (p = 0.048). Also, the level of ANXA2 trended to decrease in AML patients who had not achieving complete remission. Moreover, patients with lower expression of ANXA2 had higher death rate (p = 0.042) and shorter overall survival (HR 0.55, p = 0.042). Thus, these findings suggest that ANXA2 exerts poor prognostic effect on adult AML but favorable prognostic effect on pediatric AML. CONCLUSIONS: Collectively, Annexin family members exert distinct prognostic roles in AML, and ANXA2 can be used as a biological marker for diagnosis and prognosis of pediatric AML.


Assuntos
Anexinas/genética , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Leucemia Mieloide Aguda/genética , Masculino , Recidiva Local de Neoplasia/genética , Prognóstico , Taxa de Sobrevida
17.
J Virol Methods ; 257: 29-32, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29627335

RESUMO

Equine coital exanthema (ECE) is an infectious, venereally transmitted muco-cutaneous disease affecting mares and stallions, caused by equid alphaherpesvirus 3 (EHV3). Diagnostic tools for rapid identification of EHV3 are of primary importance to diminish the risk of EHV3 dissemination at the time of breeding. In the last years, it has been shown that the performance of the insulated-isothermal polymerase chain reaction (iiPCR) is comparable to virus isolation, nested PCR and real-time PCR (qPCR) in detecting pathogens of various animal species. Analytical sensitivity and specificity of the iiPCR were compared with a qPCR, using a plasmid containing the target region of the EHV3 glycoprotein G gene and an Argentinian EHV3 isolate (E/9283/07 C3A). In order to evaluate the diagnostic performance of the iiPCR, nucleic acids of 85 perineal and genital swabs (PGS) of mares and stallions were extracted by tacoTM mini and tested by both techniques. EHV3 was detected in 46 and 45 of the 85 PGS by the iiPCR and qPCR, respectively. There was almost perfect agreement between the two diagnostic methods (98.82%; 95% CI: 95.03-100%; κ = 0.98). The iiPCR had a limit of detection of 95.00% at 6 genome equivalents per reaction and a detection endpoint for viral DNA comparable to that of the qPCR, and did not react with six non-targeted equine pathogens. The iiPCR represents a sensitive and specific method for the rapid on-site diagnosis of EHV3 infection. Its routinely implementation in breeding facilities, and artificial insemination and embryo transfer centers, will contribute to prevent the dissemination of this venereal, highly contagious disease in horses.


Assuntos
Genitália/virologia , Infecções por Herpesviridae/veterinária , Herpesvirus Equídeo 3/isolamento & purificação , Doenças dos Cavalos/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Períneo/virologia , Reação em Cadeia da Polimerase/métodos , Animais , Infecções por Herpesviridae/diagnóstico , Doenças dos Cavalos/virologia , Cavalos , Testes Imediatos , Sensibilidade e Especificidade
18.
Genet Mol Res ; 16(3)2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-28873198

RESUMO

Cervical cancer is a serious public health problem and is associated with high cancer-related mortality in females worldwide. The expression of IL17A can increase the migration and invasiveness of cervical cancer cells by activating the NF-κB signal pathway. Single-nucleotide polymorphisms (SNPs) can alter gene function and protein expression. We examined the association between two IL17A SNPs (rs2275913 and rs3748067) and the risk of cervical cancer. We also investigated the interaction between IL17A -174G/C and -572C/G mutations and environmental factors. Our 1:2 matched case-control study included 185 cervical cancer patients and 370 healthy controls. The IL17A rs2275913 and rs3748067 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Using logistic regression analysis, we found that individuals harboring the TT genotype of IL17A rs3748067 had an increased risk of cervical cancer compared with those carrying the CC genotype, and the adjusted OR (95%CI) was 6.29 (2.30-19.81). Moreover, individuals carrying the T allele of IL17A rs3748067 were more susceptible to cervical cancer than those with the C allele, and the adjusted OR (95%CI) was 2.31 (1.53-3.50). No significant interaction was observed between the IL17A rs2275913 polymorphism and cervical cancer risk. In conclusion, our study suggests that the IL17A rs3748067 polymorphism is independently associated with the risk of cervical cancer, and has a relationship with human papillomavirus infection with regard to the risk of cervical cancer.


Assuntos
Interleucina-17/genética , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade
19.
Braz J Med Biol Res ; 50(9): e6409, 2017 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-28793059

RESUMO

This meta-analysis compared the efficacy and safety of the contact force (CF)-sensing catheter and second-generation cryoballoon (CB) ablation for treating atrial fibrillation (AF). Six controlled clinical trials comparing ablation for AF using a CF-sensing catheter or second-generation CB were identified from PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. The procedure duration was significantly lower in the CB group compared with that in the CF group [mean difference (MD)=29.4; 95%CI=17.84-40.96; P=0.01], whereas there was no difference between the groups for fluoroscopy duration (MD=0.59; 95%CI=-4.48-5.66; P=0.82). Moreover, there was no difference in the incidence of non-lethal complications (embolic event, tamponade, femoral/subclavian hematoma, arteriovenous fistula, pulmonary vein stenosis, phrenic nerve palsy, and esophageal injury) between the CB and the CF groups (8.38 vs 5.35%; RR=0.66; 95%CI=0.37-1.17; P=0.15). Transient phrenic nerve palsy occurred in 17 of 326 patients (5.2%) of the CB group vs none in the CF group (RR=0.12; 95%CI=0.03-0.43; P=0.001). A comparable proportion of patients in CF and CB groups suffered from AF recurrence during the 12-month follow-up after a single ablation procedure [risk ratio (RR)=1.03; 95%CI=0.78-1.35; P=0.84]. AF ablation using CF-sensing catheters and second-generation CB showed comparable fluoroscopy duration and efficacy (during a 12-month follow-up), with shorter procedure duration and different complications in the CB group.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Criocirurgia/métodos , Ablação por Cateter/efeitos adversos , Catéteres , Ensaios Clínicos Controlados como Assunto , Criocirurgia/efeitos adversos , Humanos
20.
Braz J Med Biol Res ; 50(8): e6204, 2017 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-28700033

RESUMO

Oxidative stress plays an important role in the development of diabetic cardiomyopathy. In the present study, we determined whether the effect of astragalus polysaccharides (APS) on diabetic cardiomyopathy was associated with its impact on oxidative stress. Streptozotocin (STZ)-induced diabetic mice and heterozygous superoxide dismutase (SOD2+/-) knockout mice were administered APS. The hemodynamics, cardiac ultrastructure, and the apoptosis, necrosis and proliferation of cardiomyocytes were assessed to evaluate the effect of APS on diabetic and oxidative cardiomyopathy. Furthermore, H2O2 formation, oxidative stress/damage, and SOD activity in cardiomyocytes were evaluated to determine the effects of APS on cardiac oxidative stress. APS therapy improved hemodynamics and myocardial ultrastructure with reduced apoptosis/necrosis, and enhanced proliferation in cardiomyocytes from both STZ-induced diabetic mice and heterozygous SOD2+/- knockout mice. In addition, APS therapy reduced H2O2 formation and oxidative stress/damage, and enhanced SOD activity in both groups of mice. Our findings suggest that APS had benefits in diabetic cardiomyopathy, which may be partly associated with its impact on cardiac oxidative stress.


Assuntos
Astrágalo/química , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Superóxido Dismutase/genética , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Estreptozocina
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