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1.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(5): 654-660, 2020 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-32897219

RESUMO

OBJECTIVE: To investigate the effect of ß-arrestin1 overexpression on tumor progression in a NCG mouse model bearing T-cell acute lymphocytic leukemia (T-ALL) Molt-4 cell xenograft. METHODS: Molt-4 cells were tagged with firefly-luciferase (F-Luc) by lentiviral infection, and fluorescence intensity of the cells was detected using a luminescence detector. Molt-4 cell lines with ß-arrestin1 overexpression or knockdown were constructed by lentivirus infection and injected via the tail vein in sub-lethal irradiated NCG mice. Body weight changes and survival time of the xenografted mice were observed, and the progression of T-ALL in the mice was evaluated using an in vivo fluorescence imaging system. Sixteen days after xenografting, the mice were euthanatized and tumor cell infiltration was observed in the slices of the liver and spleen. RESULTS: We successfully tagged Molt-4 cells with F-Luc and overexpressed or knocked down ß-arrestin1 in the tagged cells. Bioluminescent imaging showed obvious luminescence catalyzed by F-Luc in Molt-4 cells. After injection of Molt-4-Luc cells into irradiated NCG mice, a gradual enhancement of luminescence in the xenografted mice was observed over time, while the body weight of the mice decreased. Compared with the control mice, the mice xenografted with ß-arrestin1-overexpressing Molt-4 cells had significantly prolonged survival time (P < 0.001), while the survival time of the mice xenografted with Molt-4 cells with ß- arrestin1 knockdown was significantly shortened (P < 0.001). Histological examination revealed fewer infiltrating tumor cells in the liver and spleen of the mice xenografted with ß-arrestin1-overexpressing Molt-4 cells in comparison with the mice bearing parental Molt-4 cell xenografts. CONCLUSIONS: ß-arrestin1 overexpression suppresses tumor progression in mice bearing Molt-4 cell xenograft.


Assuntos
Linfócitos T , Animais , Progressão da Doença , Xenoenxertos , Humanos , Camundongos , Transplante Heterólogo , beta-Arrestina 1
2.
Acta Cir Bras ; 35(8): e202000801, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32901678

RESUMO

PURPOSE: To evaluate the use of demineralized bone matrix of caprine origin in experimental bone defects of the tibia in New Zealand rabbits. METHODS: Fragments of the tibia diaphysis were collected aseptically from clinically healthy goats. The bones were sectioned into 1 cm fragments and stored at -20°C for subsequent hydrochloric acid (HCL) demineralization. A 70 mg portion of DBMc was used to fill the experimental bone defects. Twenty-four female adult New Zealand rabbits were divided into 2 groups: the MG (matrix group, left tibia) and CG (control group, right tibia). Additionally, they were separated into 4 groups with 6 animals, according to the period of analysis (15, 30, 60 and 90 days postoperatively). Using microCT, volumetric parameters were evaluated: bone volume, relationship between bone volume and total volume, bone surface area, relationship between bone surface area and total volume, number of trabeculae, trabecular thickness and trabecular separation. RESULTS: There was a statistically significant difference (P<0.05) between groups considering bone volume (BV) and bone:total volume (BV/TV), on 15, 30 and 90 days postoperatively. Control group showed a statistically significant superiority (P < 0.05) considering the mean of the variables bone surface (BS), number of trabeculae (Tb.N) and between bone surface and total volume (BS/TV) at 15 and 90 days. CONCLUSIONS: Caprine demineralized bone matrix was safe and tolerable. No signs of material rejection were seen macroscopically. It is an alternative for the treatment of bone defects when autologous graft is not available or in insufficient quantities.


Assuntos
Transplante Ósseo , Cabras , Transplante Heterólogo , Animais , Matriz Óssea , Feminino , Xenoenxertos , Coelhos , Tíbia
3.
Nat Commun ; 11(1): 4147, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811837

RESUMO

Mutated receptor tyrosine kinases (MT-RTKs) such as internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3 ITD) and a point mutation KIT D816V are driver mutations for acute myeloid leukemia (AML). Clathrin assembly lymphoid myeloid leukemia protein (CALM) regulates intracellular transport of RTKs, however, the precise role for MT-RTKs remains elusive. We here show that CALM knock down leads to severely impaired FLT3 ITD- or KIT D814V-dependent cell growth compared to marginal influence on wild-type FLT3- or KIT-mediated cell growth. An antipsychotic drug chlorpromazine (CPZ) suppresses the growth of primary AML samples, and human CD34+CD38- AML cells including AML initiating cells with MT-RTKs in vitro and in vivo. Mechanistically, CPZ reduces CALM protein at post transcriptional level and perturbs the intracellular localization of MT-RTKs, thereby blocking their signaling. Our study presents a therapeutic strategy for AML with MT-RTKs by altering the intracellular localization of MT-RTKs using CPZ.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Clorpromazina/farmacologia , Leucemia Mieloide Aguda/genética , Proteínas Monoméricas de Montagem de Clatrina/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Feminino , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Monoméricas de Montagem de Clatrina/genética , Mutação Puntual , Transdução de Sinais/efeitos dos fármacos , Sequências de Repetição em Tandem/genética , Transplante Heterólogo , Adulto Jovem
4.
PLoS One ; 15(7): e0235611, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634139

RESUMO

Liquid biopsy has become widely applied in clinical medicine along with the progress in innovative technologies, such as next generation sequencing, but the origin of circulating tumor DNA (ctDNA) has not yet been precisely established. We reported bimodal peaks of long fragment circulating free DNA (cfDNA) of 5 kb and short fragment cfDNA of 170 bp in patients with advanced lung cancer, and both contained ctDNA. In this paper, we demonstrate that the total amount of cfDNA is higher when patients with lung cancer have extrathoracic metastases, and the amount of long fragment cfDNA is significantly higher in those patients. To investigate the origin of long fragment cfDNA, conditioned media isolated from lung cancer cell lines was fractionated. Long fragment cfDNA was found concomitant with extracellular vesicles (EVs), but short fragment cfDNA was not observed in any fractions. However, in peripheral blood from a metastatic animal model both fragments were detected even with those same lung cancer cell lines. In human plasma samples, long fragment cfDNA was observed in the same fraction as that from conditioned media, and short fragment cfDNA existed in the supernatant after centrifugation at 100,000g. Concentration of ctDNA in the supernatant was two times higher than that in plasma isolated by the conventional procedure. Long fragment cfDNA associated with tumor progression might therefore be released into peripheral blood, and it is possible that the long fragment cfDNA escapes degradation by co-existing with EVs. Examination of the biological characteristics of long fragment cfDNA is a logical subject of further investigation.


Assuntos
DNA Tumoral Circulante/análise , Neoplasias Pulmonares/diagnóstico , Animais , Estudos de Casos e Controles , Linhagem Celular Tumoral , DNA Tumoral Circulante/química , Meios de Cultivo Condicionados/metabolismo , Modelos Animais de Doenças , Receptores ErbB/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Frequência do Gene , Humanos , Biópsia Líquida , Pneumopatias/sangue , Pneumopatias/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Knockout , Mutação , Metástase Neoplásica , Transplante Heterólogo
5.
Nat Commun ; 11(1): 3778, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728076

RESUMO

Targeted genome editing has a great therapeutic potential to treat disorders that require protein replacement therapy. To develop a platform independent of specific patient mutations, therapeutic transgenes can be inserted in a safe and highly transcribed locus to maximize protein expression. Here, we describe an ex vivo editing approach to achieve efficient gene targeting in human hematopoietic stem/progenitor cells (HSPCs) and robust expression of clinically relevant proteins by the erythroid lineage. Using CRISPR-Cas9, we integrate different transgenes under the transcriptional control of the endogenous α-globin promoter, recapitulating its high and erythroid-specific expression. Erythroblasts derived from targeted HSPCs secrete different therapeutic proteins, which retain enzymatic activity and cross-correct patients' cells. Moreover, modified HSPCs maintain long-term repopulation and multilineage differentiation potential in transplanted mice. Overall, we establish a safe and versatile CRISPR-Cas9-based HSPC platform for different therapeutic applications, including hemophilia and inherited metabolic disorders.


Assuntos
Engenharia Celular/métodos , Edição de Genes , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/metabolismo , Animais , Sistemas CRISPR-Cas/genética , Linhagem Celular , Feminino , Regulação da Expressão Gênica , Hemofilia A/terapia , Humanos , Doenças Metabólicas/terapia , Camundongos , Regiões Promotoras Genéticas/genética , Transplante Autólogo/métodos , Transplante Heterólogo , alfa-Globinas/genética , alfa-Globinas/metabolismo
6.
Nat Commun ; 11(1): 3369, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632153

RESUMO

Induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neurons are an expected source for cell-based therapies for Parkinson's disease (PD). The regulatory criteria for the clinical application of these therapies, however, have not been established. Here we show the results of our pre-clinical study, in which we evaluate the safety and efficacy of dopaminergic progenitors (DAPs) derived from a clinical-grade human iPSC line. We confirm the characteristics of DAPs by in vitro analyses. We also verify that the DAP population include no residual undifferentiated iPSCs or early neural stem cells and have no genetic aberration in cancer-related genes. Furthermore, in vivo studies using immunodeficient mice reveal no tumorigenicity or toxicity of the cells. When the DAPs are transplanted into the striatum of 6-OHDA-lesioned rats, the animals show behavioral improvement. Based on these results, we started a clinical trial to treat PD patients in 2018.


Assuntos
Neurônios Dopaminérgicos/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Neurais/transplante , Doença de Parkinson/terapia , Transplante de Células-Tronco/métodos , Animais , Diferenciação Celular/genética , Linhagem Celular , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Macaca fascicularis , Masculino , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Ratos Nus , Transplante Heterólogo
7.
Gene ; 758: 144960, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32687947

RESUMO

As a member of the ubiquitin-specific protease (USP) family, USP22 could remove ubiquitin moieties from its target proteins to control the function of the target proteins. Accumulating studies show that USP22 essentially participates in diverse types of cancer as an oncogene-like protein. However, the roles of USP22 in human pancreatic ductal adenocarcinoma (PDAC) and the underlying mechanism are unknown. Here we report that USP22 promotes the growth of PDAC cells by promoting the expression of dual-specificity tyrosine regulated kinase 1A (DYRK1A). Our results showed that the expression levels of USP22 were up-regulated in human PDAC tissues and cell lines (BxPC-3, AsPC-1, MIA-PaCa-2, PANC-1, and CAPAN-1). Lentivirus-mediated knockdown of USP22 repressed the rate of proliferation and capacity of colony formation of BxPC3 and CAPAN1 cancer cells and USP22 overexpression promoted the proliferation and capacity of the colony formation of BxPC3 and CAPAN1 cancer cells. The further mechanism study showed that USP22 elevated the expression of the mRNA and protein levels of DYRK1A in PDAC cancer cells. Inhibition of DYRK1A with EHT-5732 or lentivirus-mediated knockdown of DYRK1A blocked the function of USP22 overexpression in the regulation of the proliferation and colony formation of PDAC cells. Taken together, our findings demonstrated that USP22 overexpression in PDAC promoted the growth of the cancer cells partially through upregulating the expression of DYRK1A.


Assuntos
Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Ubiquitina Tiolesterase/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Oncogenes/genética , Ductos Pancreáticos/patologia , RNA Mensageiro/genética , Transplante Heterólogo
9.
Tumour Biol ; 42(7): 1010428320937863, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32686600

RESUMO

Maintaining intracellular pH is crucial for preserving healthy cellular behavior and, when dysregulated, results in increased proliferation, migration, and invasion. The Na+/H+ exchanger isoform 1 is a highly regulated transmembrane antiporter that maintains pH homeostasis by exporting protons in response to intra- and extracellular signals. Activation of Na+/H+ exchanger isoform 1 is exquisitely regulated by the extracellular environment and protein cofactors, including calcineurin B homologous proteins 1 and 2. While Na+/H+ exchanger isoform 1 and calcineurin B homologous protein 1 are ubiquitously expressed, calcineurin B homologous protein 2 shows tissue-specific expression and upregulation in a variety of cancer cells. In addition, calcineurin B homologous protein 2 expression is modulated by tumorigenic extracellular conditions like low nutrients. To understand the role of calcineurin B homologous protein 2 in tumorigenesis and survival in lung cancer, we surveyed existing databases and formed a comprehensive report of Na+/H+ exchanger isoform 1, calcineurin B homologous protein 1, and calcineurin B homologous protein 2 expression in diseased and non-diseased tissues. We show that calcineurin B homologous protein 2 is upregulated during oncogenesis in many adeno and squamous carcinomas. To understand the functional role of calcineurin B homologous protein 2 upregulation, we evaluated the effect of Na+/H+ exchanger isoform 1 and calcineurin B homologous protein 2 depletion on cellular function during cancer progression in situ. Here, we show that calcineurin B homologous protein 2 functions through Na+/H+ exchanger isoform 1 to effect cell proliferation, cell migration, steady-state pHi, and anchorage-independent tumor growth. Finally, we present evidence that calcineurin B homologous protein 2 depletion in vivo has potential to reduce tumor burden in a xenograft model. Together, these data support the tumor-promoting potential of aberrant calcineurin B homologous protein 2 expression and position calcineurin B homologous protein 2 as a potential therapeutic target for the treatment of non-small cell lung cancer.


Assuntos
Calcineurina/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Trocador 1 de Sódio-Hidrogênio/metabolismo , Animais , Calcineurina/genética , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , Transplante de Neoplasias , Isoformas de Proteínas/metabolismo , Transplante Heterólogo
10.
Mol Immunol ; 124: 9-17, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32485436

RESUMO

BACKGROUND: Platelet refractoriness remains a challenging clinical dilemma although significant advancements have been made in identifying human leukocyte antigen (HLA) matched or HLA compatible units. Antiplatelet antibodies are the major risk factor for immune-mediated platelet refractoriness, yet the role of antibody-initiated complement-mediated platelet destruction remains poorly understood. STUDY DESIGN AND METHODS: Human complement-mediated opsonization and killing of platelets was assayed ex vivo using antibody-sensitized human platelets incubated with complement-sufficient human sera. A new animal model of platelet refractoriness utilizing Wistar rats transfused with human platelets is described. RESULTS: Human platelets sensitized with anti-platelet antibodies were rapidly opsonized with iC3b upon incubation in human sera. This opsonization could be completely blocked with a classical pathway complement inhibitor, PA-dPEG24. Complement activation decreased platelet viability, which was also reversible with complement inhibitor PA-dPEG24. A new rat model of platelet refractoriness was developed that demonstrated some platelet removal from the blood stream was complement mediated. CONCLUSIONS: Complement activation initiated by anti-platelet antibodies leads to complement opsonization and decreased platelet viability. A new rat model of platelet refractoriness was developed that adds a new tool for elucidating the mechanisms of platelet refractoriness.


Assuntos
Plaquetas/imunologia , Ativação do Complemento/imunologia , Modelos Animais de Doenças , Isoanticorpos/imunologia , Animais , Via Clássica do Complemento , Humanos , Masculino , Ratos , Ratos Wistar , Transplante Heterólogo
11.
PLoS One ; 15(6): e0234772, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555746

RESUMO

Glioblastoma is the most aggressive primary brain tumor leading to death in most of patients. It comprises almost 50-55% of all gliomas with an incidence rate of 2-3 per 100,000. Despite its rarity, overall mortality of glioblastoma is comparable to the most frequent tumors. The current standard treatment combines surgical resection, radiotherapy and chemotherapy with temozolomide. In spite of this aggressive multimodality protocol, prognosis of glioblastoma is poor and the median survival remains about 12-14.5 months. In this regard, new therapeutic approaches should be developed to improve the life quality and survival time of the patient after the initial diagnosis. Before switching to clinical trials in humans, all innovative therapeutic methods must be studied first on a relevant animal model in preclinical settings. In this regard, we validated the feasibility of intratumoral delivery of a holmium (Ho) microparticle suspension to an induced U87 glioblastoma model. Among the different radioactive beta emitters, 166Ho emits high-energy ß(-) radiation and low-energy γ radiation. ß(-) radiation is an effective means for tumor destruction and γ rays are well suited for imaging (SPECT) and consequent dosimetry. In addition, the paramagnetic Ho nucleus is a good asset to perform MRI imaging. In this study, five minipigs, implanted with our glioblastoma model were used to test the injectability of 165Ho (stable) using a bespoke injector and needle. The suspension was produced in the form of Ho microparticles and injected inside the tumor by a technique known as microbrachytherapy using a stereotactic system. At the end of this trial, it was found that the 165Ho suspension can be injected successfully inside the tumor with absence or minimal traces of Ho reflux after the injections. This injection technique and the use of the 165Ho suspension needs to be further assessed with radioactive 166Ho in future studies.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Hólmio/química , Compostos Radiofarmacêuticos/administração & dosagem , Siloxanas/química , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Humanos , Masculino , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Suínos , Porco Miniatura , Tomografia Computadorizada de Emissão de Fóton Único , Transplante Heterólogo
12.
J Anesth Hist ; 6(2): 70-73, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32593379

RESUMO

Leo Fabian played a role in many anesthesia firsts: the first halothane anesthetics in the United States, the first American electrical anesthetic, the first lung allotransplant, and the first heart xenotransplant. As was common for men of his generation, Fabian's first taste of medicine came during World War II, as a pharmacist's mate aboard the U.S.S. Bountiful. Afterward, he pursued his medical education before joining Dr. C. Ronald Stephen and the anesthesiology department at Duke. There he helped to create one of the first inhalers for halothane, the Fabian Newton Stephen (F-N-S) Fluothane Vaporizer. Fabian left Duke for the University of Mississippi Medical Center, where he consistently worked with the chair of surgery, Dr. James Hardy. Together they performed the first American electrical anesthetic, the first lung allotransplant, and the first heart xenotransplant. By the end of his time at Mississippi, Fabian and Hardy had several philosophical disagreements, and Fabian ultimately left for Washington University in St. Louis, where he rejoined Dr. Stephen. He served as Stephen's right-hand man and would oversee the department when Stephen was away. Fabian spent the final years of his career as chair of the department before his own health forced him to step down.


Assuntos
Anestesia/história , Anestesiologia/história , Anestesia/métodos , Anestesiologia/instrumentação , Animais , Eletricidade/história , Transplante de Coração/história , História do Século XX , Experimentação Humana/história , Humanos , Transplante de Pulmão/história , Pan troglodytes , Transplante Heterólogo/ética , Transplante Heterólogo/história , Estados Unidos
13.
PLoS One ; 15(6): e0232068, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559187

RESUMO

Cyclin Dependent Kinase 9 (CDK9) associates with Bromodomain and Extra-Terminal Domain (BET) proteins to promote transcriptional elongation by phosphorylation of serine 2 of RNAP II C-terminal domain. We examined the therapeutic potential of selective CDK9 inhibitors (AZD 4573 and MC180295) against human multiple myeloma cells in vitro. Short-hairpin RNA silencing of CDK9 in Multiple Myeloma (MM) cell lines reduced cell viability compared to control cells showing the dependency of MM cells on CDK9. In order to explore synergy with the CDK9 inhibitor, proteolysis targeting chimeric molecule (PROTAC) ARV 825 was added. This latter drug causes ubiquitination of BET proteins resulting in their rapid and efficient degradation. Combination treatment of MM cells with ARV 825 and AZD 4573 markedly reduced their protein expression of BRD 2, BRD 4, MYC and phosphorylated RNA pol II as compared to each single agent alone. Combination treatment synergistically inhibited multiple myeloma cells both in vitro and in vivo with insignificant weight loss. The combination also resulted in marked increase of apoptotic cells at low dose compared to single agent alone. Taken together, our studies show for the first time that the combination of a BET PROTAC (ARV 825) plus AZD 4573 (CDK9 inhibitor) is effective against MM cells.


Assuntos
Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas/metabolismo , Proteólise/efeitos dos fármacos , Animais , Azepinas/farmacologia , Azepinas/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quinase 9 Dependente de Ciclina/genética , Quinase 9 Dependente de Ciclina/metabolismo , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Camundongos , Camundongos SCID , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Polimerase II/metabolismo , RNA Interferente Pequeno/metabolismo , Talidomida/análogos & derivados , Talidomida/farmacologia , Talidomida/uso terapêutico , Transplante Heterólogo
14.
Khirurgiia (Mosk) ; (5): 93-95, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32500696

RESUMO

Long-term outcome of surgical treatment of a patient with severe aortic insufficiency and ascending aortic aneurysm is reported. The patient underwent Bentall-DeBono procedure with xenopericardial valved conduit. This technique is associated with no complications specific for Dacron conduits and ensures clinical compensation of heart failure, improves prognosis and quality of life.


Assuntos
Aneurisma Aórtico/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Pericárdio/transplante , Prótese Vascular , Implante de Prótese Vascular , Seguimentos , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca , Humanos , Qualidade de Vida , Transplante Heterólogo
16.
Virulence ; 11(1): 486-488, 2020 12.
Artigo em Inglês | MEDLINE | ID: covidwho-327357

RESUMO

Lack of an appropriate animal model to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for COVID-19 pandemic disease, represents a significant hurdle in the process of understanding disease biology and evaluating therapeutic and preventive candidates. It is time for public health agencies to revisit regulation on transplantation of human pluripotent stem cells for the possibility of the development of a humanized mice model with a humanized lung.


Assuntos
Infecções por Coronavirus/patologia , Modelos Animais de Doenças , Células-Tronco Pluripotentes/transplante , Pneumonia Viral/patologia , Infecções Respiratórias/patologia , Transplante Heterólogo/legislação & jurisprudência , Animais , Humanos , Camundongos , Pandemias , Pesquisa/legislação & jurisprudência , Pesquisa/normas , Pesquisa/tendências , Transplante Heterólogo/tendências
17.
Braz. J. Vet. Res. Anim. Sci. (Online) ; 57(2): [e161756], mai. 2020. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1097353

RESUMO

An Andean fox was transferred to the Wildlife Hospital of the Universidad San Francisco de Quito for evaluation of injuries caused by a run over. Clinical signs of hypovolemic shock were detected. Radiographies showed multiple pelvic fractures and free fluid in retroperitoneal cavity. The presumptive diagnosis was hemorrhagic shock caused by blood loss secondary to a pelvis fracture. An emergency xenotransfusion using blood from a domestic dog was performed without acute transfusion reactions observed. This is the first report of successful xenotransfusion between a domestic dog and an Andean fox presenting a procedure that could be applied in emergency situations.(AU)


Uma raposa andina foi levada ao Hospital da Vida Selvagem da Universidad San Francisco de Quito para avaliar os ferimentos causados por um atropelamento. Sinais clínicos de choque hipovolêmico foram detectados. Radiografias mostraram múltiplas fraturas pélvicas e fluido livre na cavidade retroperitoneal. O diagnóstico presuntivo foi um choque hemorrágico causado por perda sanguínea secundária a uma fratura pélvica. Uma xenotransfusão de emergência foi realizada com o sangue de um cão doméstico sem reações agudas transfusionais. Este é o primeiro relato bem sucedido de xenotransfusão entre um cão doméstico e uma raposa andina, demonstrando que é um procedimento que poderá ser considerado em situações de emergência.(AU)


Assuntos
Animais , Cães , Cães/sangue , Raposas/sangue , Choque , Transplante Heterólogo , Transfusão de Sangue/veterinária
19.
Invest Ophthalmol Vis Sci ; 61(5): 31, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32428232

RESUMO

Purpose: More recently, literature has emerged providing findings about the novelty of microRNAs (miR)-targeted therapeutics in the treatment of retinoblastoma (RB). The prime objective of this study was to identify the potential role of miR-378a-3p and its regulation in RB cells via forkhead box G1 (FOXG1). Methods: The expression of miR-378a-3p and FOXG1 in the clinical RB tissues was determined using RNA quantitation and Western blot assays. The interaction between miR-378a-3p and FOXG1 was identified using dual luciferase reporter gene assay. The potential effects of miR-378a-3p on the RB cell biological processes were evaluated by conducting gain- and loss-of-function studies of miR-378a-3p and FOXG1, followed by cell viability, cell cycle progression, and apoptosis measurements. Furthermore, experiments were performed in nude mice to assess its effects on tumor formation. Results: miR-378a-3p was poorly expressed, whereas FOXG1 was highly expressed in RB tissues and cells. miR-378a-3p bound to the FOXG1 3' untranslated region and negatively modulated its expression. The overexpression of miR-378a-3p was found to decrease RB cell viability and to promote cell apoptosis in vitro, whereas overexpressed FOXG1 reversed the regulatory effects of miR-378a-3p on RB cellular behaviors. In nude mice, the restoration of miR-378a-3p by miR-378a-3p agomir was shown to play a role in the reduction of tumor volume and size relative to nude mice injected with negative control-agomir. Conclusions: Our findings identified that increased miR-378a-3p exerted an inhibitory effect on RB cell proliferation by targeting FOXG1, suggesting the role of miR-378a-3p as a novel therapeutic target for RB.


Assuntos
Apoptose , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , MicroRNAs/fisiologia , Proteínas do Tecido Nervoso/genética , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Animais , Western Blotting , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Pré-Escolar , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Perfilação da Expressão Gênica , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas do Tecido Nervoso/metabolismo , Plasmídeos/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias da Retina/metabolismo , Retinoblastoma/metabolismo , Organismos Livres de Patógenos Específicos , Transfecção , Transplante Heterólogo , Células Tumorais Cultivadas
20.
Virulence ; 11(1): 486-488, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32434416

RESUMO

Lack of an appropriate animal model to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for COVID-19 pandemic disease, represents a significant hurdle in the process of understanding disease biology and evaluating therapeutic and preventive candidates. It is time for public health agencies to revisit regulation on transplantation of human pluripotent stem cells for the possibility of the development of a humanized mice model with a humanized lung.


Assuntos
Infecções por Coronavirus/patologia , Modelos Animais de Doenças , Células-Tronco Pluripotentes/transplante , Pneumonia Viral/patologia , Infecções Respiratórias/patologia , Transplante Heterólogo/legislação & jurisprudência , Animais , Humanos , Camundongos , Pandemias , Pesquisa/legislação & jurisprudência , Pesquisa/normas , Pesquisa/tendências , Transplante Heterólogo/tendências
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