Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 15.258
Filtrar
1.
Life Sci ; 257: 118052, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32634431

RESUMO

AIMS: Granulocyte colony-stimulating factor (G-CSF) is a cytokine that induces proliferation and differentiation of hematopoietic precursor cells and activation of mature neutrophils. G-CSF is overexpressed in several malignant tumors and blocking its binding to the receptor can lead to significant decrease in tumor growth, vascularization and metastasis. Furthermore, targeting G-CSF receptor has shown therapeutic benefit in other diseases such as rheumatoid arthritis, progressive neurodegenerative disorder and uveitis. Camelid single-chain antibodies (nanobodies) have exceptional properties making them appropriate for tumor imaging and therapeutic application. In this study we aim to use the rational design approach to engineer a previously described G-CSF-R targeting nanobody (VHH1), to improve its affinity toward G-CSF-R. MAIN METHODS: We redesigned the complementary determining region 3 (CDR3) domain of the VHH1 nanobody to mimic G-CSF interaction to its receptor and developed five new engineered nanobodies. Binding affinity of the engineered nanobodies was evaluated by ELISA (Enzyme-linked immunosorbent assay) on NFS60 cells. KEY FINDINGS: Enzyme-linked immunosorbent assay (ELISA) confirmed the specificity of the engineered nanobodies and ELISA-based determination of affinity revealed that two of the engineered nanobodies (1c and 5a) bind to G-CSF-R on the surface of NFS60 cells in a dose-dependent manner and with a higher potency compared to the parental nanobody. SIGNIFICANCE: Additional studies are required to better characterize these nanobodies and assess their interaction with G-CSF-R in vitro and in vivo. These newly developed nanobodies could be beneficial in tumor imaging and therapy and make a basis for development of additional engineered nanobodies.


Assuntos
Fator Estimulador de Colônias de Granulócitos/ultraestrutura , Receptores de Fator Estimulador de Colônias de Granulócitos/imunologia , Anticorpos de Domínio Único/imunologia , Anticorpos , Anticorpos Monoclonais/imunologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia de Afinidade/métodos , Ensaio de Imunoadsorção Enzimática , Fator Estimulador de Colônias de Granulócitos/imunologia , Fator Estimulador de Colônias de Granulócitos/metabolismo , Humanos , Neovascularização Patológica/tratamento farmacológico , Engenharia de Proteínas/métodos , Anticorpos de Cadeia Única
2.
Nihon Shokakibyo Gakkai Zasshi ; 117(7): 626-634, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32655122

RESUMO

An 82-year-old male with a gallbladder mass was diagnosed with gallbladder carcinoma through various examinations. Cholecystectomy, gallbladder bed resection, and lymph node dissection were performed. The histological examination revealed a gallbladder adenosquamous carcinoma, and this tumor showed positive staining for granulocyte-colony stimulating factor (G-CSF). Recurrence of multiple liver metastases was detected on 25th day postoperatively. Unfortunately, the patient died on 97th day postoperatively. Here, we report a case of G-CSF-producing adenosquamous carcinoma of the gallbladder with rapid recurrence of liver metastases in the early postoperative period.


Assuntos
Carcinoma Adenoescamoso , Neoplasias da Vesícula Biliar , Neoplasias Hepáticas , Idoso de 80 Anos ou mais , Fator Estimulador de Colônias de Granulócitos , Granulócitos , Humanos , Masculino , Recidiva Local de Neoplasia
4.
Cancer Treat Rev ; 89: 102071, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32717620

RESUMO

Haplo-identical transplant is being increasingly used in patients who do not have a readily available matched related or unrelated donor. Post-transplant cyclophosphamide's use due to its simplicity and documented efficacy has made this approach readily employable across diverse transplant centres across the globe. The outcomes of regimens used for conditioning in recipients of bone marrow are at times in variance to that from more commonly employed G-CSF mobilised peripheral stem cell (PBSC). This review highlights various conditioning regimens used in PBSC recipients, with emphasis on toxicities, practicalities and transplant related outcomes of relapse, non-relapse mortality and graft versus host disease.


Assuntos
Ciclofosfamida/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/farmacologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Células-Tronco de Sangue Periférico/efeitos dos fármacos , Condicionamento Pré-Transplante/métodos , Haplótipos , Mobilização de Células-Tronco Hematopoéticas/métodos , Imunossupressores/administração & dosagem , Células-Tronco de Sangue Periférico/citologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante Homólogo
6.
Tumori ; 106(4): 273-280, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32538316

RESUMO

Neutropenia is the most frequent side effect of commercially available myelosuppressive drugs and its most significant complication is febrile neutropenia. It is associated with increased hospital admissions and higher probability of death. Prophylaxis with the administration of granulocyte colony-stimulating factor can prevent neutropenia caused by anticancer drugs. The correct administration of these drugs and the management of febrile neutropenia are extremely important in the treatment of patients with cancer.


Assuntos
Antineoplásicos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias/tratamento farmacológico , Neutropenia/tratamento farmacológico , Antineoplásicos/uso terapêutico , Gerenciamento Clínico , Guias como Assunto , Humanos , Quimioterapia de Indução/efeitos adversos , Neoplasias/complicações , Neoplasias/patologia , Neutropenia/induzido quimicamente , Neutropenia/patologia
7.
Cell Prolif ; 53(7): e12824, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32567730

RESUMO

OBJECTIVES: Bone marrow edema is a universal manifestation of rheumatoid arthritis (RA), and its pathological essence is a bone marrow lesion (BML) formed by various bone marrow (BM) immune cells. Neutrophils play an important role in inflammatory arthritis, but the role and mechanism of neutrophils in BML are not clear. MATERIALS AND METHODS: Granulocyte colony-stimulating factor (G-CSF) -/- mice and wild type (WT) C57BL/6 mice were immunized for collagen-induced arthritis (CIA). Histological scores of arthritis were evaluated. Immunohistochemistry staining with anti-Ly6G was conducted. Neutrophil extracellular traps (NETs) in joint sections were determined by immunofluorescence staining. BM neutrophils were isolated for flow cytometry and NETosis induction in vitro. RESULTS: Histological study showed significant neutrophil infiltrations in BML of CIA mice. Inhibition of BM neutrophil production by G-CSF knock out can obstruct the induction of BML and CIA. In addition to abundant infiltrated NETs intra-articular, remarkable NETosis primed BM neutrophils were infiltrated in BML of CIA mice, which was positively related to bone erosion. Neutrophils derived from G-CSF-/- mice have diminished ability of NETs formation in vitro, while G-CSF induction can enhance its capacity of NETs formation. CONCLUSIONS: We propose for the first time that the overproduced BM neutrophils in CIA mice are primed for NETosis in a G-CSF dependent manner, and these pathogenic cells may have an important role in inflammatory arthritis. Blocking this pathological process could be a potential strategy for the treatment of RA.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Medula Óssea/imunologia , Neutrófilos/imunologia , Animais , Células da Medula Óssea/imunologia , Colágeno/imunologia , Armadilhas Extracelulares/imunologia , Fator Estimulador de Colônias de Granulócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL
9.
J Infect Dis ; 222(5): 746-754, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32563194

RESUMO

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe, and convalescent SARS-CoV-2-infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1α were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were significantly higher in SARS-CoV-2-infected male than female patients. The serum levels of MCP-1, G-CSF, and VEGF were weakly and positively correlated with viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluation of the severity of COVID-19 and optimize the therapeutic strategies.


Assuntos
Quimiocinas/sangue , Infecções por Coronavirus/sangue , Citocinas/sangue , Pneumonia Viral/sangue , Adulto , Betacoronavirus/isolamento & purificação , Quimiocina CCL2/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/sangue , Carga Viral
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 828-832, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552943

RESUMO

OBJECTIVE: To study the efficacy of small dose HAG combined with decitabine regimen in the treatment of elderly patients with acute myeloid leukemia (AML). METHODS: 134 elderly AML patients treated in our hospital from March 2015 to December 2018 were selected, and the patients were divided into CAG group and combined treatment group. The AML patients in CAG group was treated with CAG regimen, while the AML patients in combined treatment group was treated with small dose HAG regimen combined with decitabine. Efficacy was evaluated after treatment. RESULTS: After treatment, the OR rate of the patients in combined treatment group was significantly higher than that in CAG group (χ2=5.311, P=0.021). The nausea and vomiting rate, infection rate, myelosuppression rate, bleeding rate and intestinal discomfort rate showed no significant difference between the two groups (P>0.05). The CD3+, CD4+ and CD8+ levels of patients in combined treatment group were significantly lower than those in CAG group (P<0.05). The result of followed-up for 2 years, showed that the overall survival rate of patients in combined treatment group was significantly higher than that in CAG group [(76.2±6.3)% vs (45.7±7.6)%] (χ2=4.214, P<0.05), while the disease free survival rate of patients in combined treatment group were (57.4±7.7)%, which was significantly higher than that in CAG group (30.3±7.9)% (χ2=5.250, P<0.05). CONCLUSION: Small dose HAG regimen combined with decitabine for elderly patients with acute myeloid leukemia has a certain curative efficacy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda , Idoso , Citarabina , Decitabina , Intervalo Livre de Doença , Fator Estimulador de Colônias de Granulócitos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Taxa de Sobrevida , Resultado do Tratamento
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 894-898, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552954

RESUMO

OBJECTIVE: To investigate the influence of conventional CAG regimen and decitabine + decreased dose CAG (D+dCAG) regimen on the clinical efficacy and safety of patients with MDS-RAEB/AML-MRC. METHODS: The clinical data of 67 patients with MDS-RAEB/AML-MRC hospitalized in our hospital from March 2012 to July 2017 were analyzed retrospectively. According to chemotherapecctic regimens, 76 patients were divided into 2 groups: 37 patients treated with conventional CAG regimen were enrolled in control group, 30 patients treated with decitabine + decreased dose CAG regimen were enrolled in D+dCAG group. The complete remission (CR) rate, overall remission rate (ORR), OS and PFS time and incidence of adverse reactions in 2 groups were compared. RESULTS: The CR in D+dCAG group was significantly higher than that in control group (P<0.05). ORR was not significanly different between 2 groups (P>0.05). There was no significant difference in the cumulative OS rate between 2 groups (P>0.05). There was no significant difference in the cumulative OS rate and PFS rate in nonimplantation between 2 groups (P>0.05). The incidence of adverse reactions of hematological system, pulmonary infection, skin and soft tissue infection, agranulocytosic fever and mycotic infection was not significanly different between 2 groups (P>0.05). The duration of granulocyte deficiency and platelet count less than 20×109/L were not significanly different between 2 groups (P>0.05). CONCLUSION: Compared with conventional CAG regimen, decitabine + decreased dose CAG regimen in the treatment of patients with MDS-RAEB/AML-MRC can efficiently improve the remission effects and showed the well overall safety, but can not increase the survival rate.


Assuntos
Anemia Refratária com Excesso de Blastos , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Decitabina , Fator Estimulador de Colônias de Granulócitos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
13.
Bull Cancer ; 107(6): 629-632, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-155023

RESUMO

Since the emergence of the SARS-CoV-2 infection, many recommendations have been made. However, the very nature of acute lymphoblastic leukemias and their treatment in children and adolescents led the Leukemia Committee of the French Society for the fight against cancers and leukemias in children and adolescents (SFCE) to propose more specific recommendations, even if data for this population are still scarce. They may have to evolve according to the rapid evolution of knowledge on COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/farmacocinética , Antivirais/uso terapêutico , Criança , Técnicas de Laboratório Clínico , Terapia Combinada , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Gerenciamento Clínico , Síndrome de Down/epidemiologia , Interações Medicamentosas , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/prevenção & controle , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Indução de Remissão , Risco , Medição de Risco , Terapia de Salvação , Avaliação de Sintomas
14.
Gan To Kagaku Ryoho ; 47(5): 851-853, 2020 May.
Artigo em Japonês | MEDLINE | ID: mdl-32408335

RESUMO

BACKGROUND: Pegfilgrastim, a long-acting granulocyte-colony-stimulating factor(G-CSF), has been used as prophylaxis for severe hematotoxicity induced by chemotherapy. We report a case of aortitis induced by pegfilgrastim administration during modified FOLFIRINOX(mFOLFIRINOX)chemotherapy for metastatic pancreatic cancer. CASE REPORT: A 65-year-old woman underwent a distal pancreatectomy for pancreatic tail cancer. Liver metastases appeared 2 years after the surgery. mFOLFIRINOX chemotherapy was started with prophylactic administration of pegfilgrastim. Eight days after the first administration and 6 days after administration of the 8th course, the patient developed a fever. The blood test results indicated severe inflammation. Computed tomography revealed a thickened aorta indicating aortitis. The symptoms rapidly improved with antibiotic therapy. We diagnosed aortitis induced by pegfilgrastim administration. CONCLUSION: Aortitis should be considered when a patient has unidentified inflammatory findings after receiving pegfilgrastim.


Assuntos
Aortite , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Neoplasias Pancreáticas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Aortite/induzido quimicamente , Feminino , Filgrastim , Granulócitos , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Polietilenoglicóis , Proteínas Recombinantes
15.
Bull Cancer ; 107(6): 629-632, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32387061

RESUMO

Since the emergence of the SARS-CoV-2 infection, many recommendations have been made. However, the very nature of acute lymphoblastic leukemias and their treatment in children and adolescents led the Leukemia Committee of the French Society for the fight against cancers and leukemias in children and adolescents (SFCE) to propose more specific recommendations, even if data for this population are still scarce. They may have to evolve according to the rapid evolution of knowledge on COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/farmacocinética , Antivirais/uso terapêutico , Criança , Técnicas de Laboratório Clínico , Terapia Combinada , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Gerenciamento Clínico , Síndrome de Down/epidemiologia , Interações Medicamentosas , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/prevenção & controle , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Indução de Remissão , Risco , Medição de Risco , Terapia de Salvação , Avaliação de Sintomas
16.
PLoS One ; 15(5): e0233738, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470072

RESUMO

Sepsis is an important cause of morbidity and mortality in pediatric patients. Increased expression of olfactomedin-4 (OLFM4), a glycoprotein contained within a subpopulation of neutrophils, has been associated with complicated course in sepsis. The factors that regulate OLFM4 expression are unknown. Here, we followed children undergoing bone marrow transplantation (BMT) to document the percentage of neutrophils that express OLFM4 over time. This population was selected because of the ability to observe nascent neutrophils following engraftment, perform frequent blood sampling, and the children are at high risk for clinical complications that may associate with changes in percentage of OLFM4+ neutrophils. We found a surprising degree of variability of OLFM4 expression between patients. In the weeks following initial neutrophil recovery we also saw great variability in OLFM4 expression within individual patients, indicating that multiple external factors may modify OLFM4 expression. We identified decreased expression of CD64 (a marker associated with response to infection), in OLFM4+ neutrophils. This is the first study to demonstrate fluctuation in OLFM4 expression within patients and provides insight into possible mechanisms for OLFM4 regulation in nascent neutrophils.


Assuntos
Biomarcadores/metabolismo , Transplante de Medula Óssea/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/metabolismo , Neutrófilos/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Neutrófilos/patologia , Receptores de IgG/metabolismo , Sepse/etiologia , Sepse/metabolismo , Adulto Jovem
18.
PLoS One ; 15(5): e0233751, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470079

RESUMO

Mesenchymal stromal cells are an important component of the bone marrow hematopoietic niche. Prior studies showed that signaling from members of the transforming growth factor (TGF) superfamily in mesenchymal stromal cells is required for normal niche development. Here, we assessed the impact of TGF family signaling on niche maintenance and stress responses by deleting Smad4 in mesenchymal stromal cells at birth, thereby abrogating canonical TGF signaling. No alteration in the number or spatial organization of CXCL12-abundant reticular (CAR) cells, osteoblasts, or adipocytes was observed in Osx-Cre, Smad4fl/fl mice, and expression of key niche factors was normal. Basal hematopoiesis and stress erythropoiesis responses to acute hemolytic anemia were normal. TGF-ß potently inhibits stromal CXCL12 expression in vitro; however, G-CSF induced decreases in bone marrow CXCL12 expression and subsequent hematopoietic stem/progenitor cell mobilization were normal in Osx-Cre, Tgfbr2fl/fl mice, in which all TGF-ß signaling in mesenchymal stromal is lost. Finally, although a prior study showed that TGF-ß enhances recovery from myeloablative therapy, hematopoietic recovery following single or multiple doses of 5-flurauracil were normal in Osx-Cre, Tgfbr2fl/fl mice. Collectively, these data suggest that TGF family member signaling in mesenchymal stromal cells is dispensable for hematopoietic niche maintenance under basal and stress conditions.


Assuntos
Anemia Hemolítica/metabolismo , Eritropoese , Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Fator de Crescimento Transformador beta/fisiologia , Fatores de Crescimento Transformadores/fisiologia , Doença Aguda , Anemia Hemolítica/patologia , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Células Cultivadas , Quimiocina CXCL12/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/patologia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Nicho de Células-Tronco
19.
Nat Commun ; 11(1): 2031, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341348

RESUMO

Neutrophils employ several mechanisms to restrict fungi, including the action of enzymes such as myeloperoxidase (MPO) or NADPH oxidase, and the release of neutrophil extracellular traps (NETs). Moreover, they cooperate, forming "swarms" to attack fungi that are larger than individual neutrophils. Here, we designed an assay for studying how these mechanisms work together and contribute to neutrophil's ability to contain clusters of live Candida. We find that neutrophil swarming over Candida clusters delays germination through the action of MPO and NADPH oxidase, and restricts fungal growth through NET release within the swarm. In comparison with neutrophils from healthy subjects, those from patients with chronic granulomatous disease produce larger swarms against Candida, but their release of NETs is delayed, resulting in impaired control of fungal growth. We also show that granulocyte colony-stimulating factors (GCSF and GM-CSF) enhance swarming and neutrophil ability to restrict fungal growth, even during treatment with chemical inhibitors that disrupt neutrophil function.


Assuntos
Candida albicans/crescimento & desenvolvimento , Neutrófilos/citologia , Neutrófilos/microbiologia , Sistemas CRISPR-Cas , Candidíase/microbiologia , Linhagem Celular , Armadilhas Extracelulares/metabolismo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Doença Granulomatosa Crônica/microbiologia , Humanos , Processamento de Imagem Assistida por Computador , Análise em Microsséries , NADPH Oxidases/metabolismo , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo
20.
J Anim Sci ; 98(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32277240

RESUMO

Colony-stimulating factor 3 (CSF3), also known as granulocyte colony-stimulating factor, is used to reduce the incidence of mastitis in cattle. Here, we tested whether recombinant bovine CSF3 at 1, 10, or 100 ng/mL acts on the bovine oocyte during maturation or on the developing embryo to modify competence for development and characteristics of the resultant blastocyst. For experiment 1, oocytes were matured with or without CSF3. The resultant embryos were cultured in a serum-free medium for 7.5 d. There was no effect of CSF3 on cleavage or on development to the blastocyst stage except that 100 ng/mL reduced the percent of putative zygotes and cleaved embryos becoming blastocysts. Expression of transcripts for 93 genes in blastocysts was evaluated by RT-PCR using the Fluidigm platform. Transcript abundance was affected by one or more concentrations of CSF3 for four genes only (CYP11A1, NOTCH2, RAC1, and YAP1). For experiment 2, cumulus-oocyte complexes (COC) were fertilized with either X- or Y-sorted semen. Putative zygotes were cultured in medium containing CSF3 treatments added at the beginning of culture. There was no effect of CSF3, sex, or the interaction on the percent of putative zygotes that cleaved or on the percent of putative zygotes or cleaved embryos becoming a blastocyst. For experiment 3, CSF3 was added from day 4 to 7.5 of development. There was no effect of CSF3 on development to the blastocyst stage. Transcript abundance of 10 genes was increased by 100 ng/mL CSF3, including markers of epiblast (NANOG, SOX2), hypoblast (ALPL, FN1, KDM2B, and PDGFRA), epiblast and hypoblast (HNF4A) and trophectoderm (TJAP1). Results are indicative that concentrations of CSF3 higher than typical after therapeutic administration can reduce oocyte competence and act on the embryo to affect characteristics of the blastocyst.


Assuntos
Bovinos/embriologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Reprodução/efeitos dos fármacos , Animais , Blastocisto/efeitos dos fármacos , Embrião de Mamíferos/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Fertilização In Vitro/veterinária , Oócitos/efeitos dos fármacos , Proteínas Recombinantes
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA