RESUMO
BACKGROUND: The aim was to explore the treatment of a case of congenital thrombotic thrombocytopenic purpura induced by pregnancy complicated with cerebral vasospasm. METHODS: We present a case study of congenital TTP where disease onset occurred during two separate pregnancies. Interestingly, the disease course exhibited distinct differences on each occasion. Additionally, following plasma transfusion therapy, there was a transient occurrence of cerebral vasospasm. RESULTS: In this case, ADAMTS13 levels reached their lowest point three days after delivery during the first pregnancy, triggering morbidity. Remarkably, a single plasma transfusion of 400 mL sufficed for the patient's recovery. Nonetheless, a recurrence of symptoms transpired during her second pregnancy at 24 weeks of gestation. Plasma transfusions were administered during and after delivery. Sudden convulsions developed. ADAMTS13 ac-tivity returned to normal, but cranial MRA revealed constrictions in the intracranial segments of both vertebral arteries, the basilar artery, and the lumen of the anterior, middle, and posterior cerebral arteries. A subsequent cranial MRA conducted a month later showed no lumen stenosis, indicating spontaneous recovery. CONCLUSIONS: These findings highlight the importance of careful consideration when administering plasma transfusions in congenital TTP during pregnancy. Moreover, the development of novel therapeutic approaches such as recombinant ADAMTS13 is crucial for minimizing complications and optimizing patient care.
Assuntos
Complicações Hematológicas na Gravidez , Púrpura Trombocitopênica Trombótica , Vasoespasmo Intracraniano , Humanos , Gravidez , Feminino , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/terapia , Transfusão de Componentes Sanguíneos/efeitos adversos , Vasoespasmo Intracraniano/complicações , Vasoespasmo Intracraniano/terapia , PlasmaRESUMO
BACKGROUND: The aim was to determine the clinical role of long non coding maternally expressed gene 3 (lncRNA MEG3) in adult acute myeloid leukemia (AML). METHODS: The expression levels of lncRNA MEG3 in bone marrow of AML patients and healthy donors were determined by qPCR. The correlation between expression levels of lncRNA MEG3 and clinical features was also analyzed. MTT assay and flow-cytometric assay were employed to determine the role of lncRNA MEG3 on the cell viability and apoptosis of AML cell lines. Expression levels of caspase-9, Bcl-2, MDM2, and p53 in those cells were determined by western blot. RESULTS: The expression levels of lncRNA MEG3 was significantly down-regulated in AML patients. Expression levels of lncRNA MEG3 were positively correlated with overall survival of patients. Up-regulation of lncRNA MEG3 could not only inhibit the cell growth and promoted apoptosis, but also increased the expression of caspase-9 and p53 and decreased the expression of Bcl-2 and MDM2. CONCLUSIONS: These results suggest that down-regulation of lncRNA MEG3 in AML patients might promote tumor progression and affect the p53-MDM2 pathway.
Assuntos
Leucemia Mieloide Aguda , RNA Longo não Codificante , Adulto , Humanos , Caspase 9 , RNA Longo não Codificante/genética , Proteína Supressora de Tumor p53/genética , Leucemia Mieloide Aguda/genética , Apoptose/genética , Proteínas Proto-Oncogênicas c-mdm2/genéticaRESUMO
BACKGROUND: CircPVT1's effects and mechanisms of acute lymphoblastic leukemia were explored in this research. METHODS: Real-time fluorescent quantitative PCR was utilized to test circPVT1 and miR-125b in ALL samples and ALL cell systems. Dual luciferase reporter assay verified the combination of circPVT1 and miR-125b. We utilized circPVAT1 as well as miR-125b's over-expression and low-expression to prove their influence on cell proliferation and invading. RESULTS: We found that more expression of circPVT1 occurred in ALL samples and ALL cell systems. CircPVT1 over-expression promoted ALL cell proliferation and migration besides invading. CircPVT1 low expression inhibited ALL cell proliferation and migration besides invading. MiR-125b was a target combination of circPVT1. CircPVT1 was able to enhance NF-κB signal pathway's expression through reducing miR-125b. CONCLUSIONS: CircPVT2 can promote ALL cell proliferation and invading through miR-125b modulation of NF-κB, which would be one new potential target for ALL therapy.
Assuntos
MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proliferação de Células , Humanos , MicroRNAs/genética , NF-kappa B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , RNA Circular , Transdução de SinaisRESUMO
Previous mutational analyses of naturally occurring West Nile virus (WNV) strains and engineered mutant WNV strains have identified locations in the viral genome that can have profound phenotypic effect on viral infectivity, temperature sensitivity and neuroinvasiveness. We chose six mutant WNV strains to evaluate for vector competence in the natural WNV vector Culex tarsalis, two of which contain multiple ablations of glycosylation sites in the envelope and NS1 proteins; three of which contain mutations in the NS4B protein and an attenuated natural bird isolate (Bird 1153) harbouring an NS4B mutation. Despite vertebrate attenuation, all NS4B mutant viruses displayed enhanced vector competence by Cx. tarsalis. Non-glycosylated mutant viruses displayed decreased vector competence in Cx. tarsalis mosquitoes, particularly when all three NS1 glycosylation sites were abolished. These results indicate the importance of both the NS4B protein and NS1 glycosylation in the transmission of WNV by a significant mosquito vector.
Assuntos
Culex/virologia , Insetos Vetores/virologia , Vertebrados/virologia , Proteínas não Estruturais Virais/genética , Febre do Nilo Ocidental/transmissão , Vírus do Nilo Ocidental/fisiologia , Animais , Feminino , Glicosilação , Mutação , Temperatura , Estados Unidos , Proteínas não Estruturais Virais/metabolismo , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/genética , Vírus do Nilo Ocidental/patogenicidadeRESUMO
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer with dismal prognosis. Recent studies disclosed that circPVT1 played an oncogene role in various cancers. But its role in T-ALL is still unclear. In this study, we found the expression levels of circPVT1 in bone marrows and cell lines of T-ALL were significantly up regulated and knock-down of circPVT1 in T-ALL cell lines could inhibit the cell proliferation and increase the cell apoptosis. Further analysis showed that circPVT1 could bind directly to miR-30e and contributed to the activate the Notch signaling by regulating miR-30e/DLL4 pathway. The levels of circPVT1 were obviously related to cumulative relapse rate and 5-year survival rate. In conclusion, our study reveals that circPVT1 participates in the progression of T-ALL through the miR-30e/DLL4 pathway and might represent a potential therapeutic target for T-ALL treatment.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proliferação de Células/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Apoptose/genética , Apoptose/fisiologia , Proliferação de Células/fisiologia , Humanos , MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , RNA Circular/imunologia , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Regulação para CimaRESUMO
Multiple myeloma (MM) is a plasma cells malignant proliferative disease, especially in aged people. LncRNAs have been considered as important regulators in MM. This research was to study the effect of LncRNA MALAT1 on the proliferation and adhesion of myeloma cells and whether Long non-coding RNAs MALAT1(LncRNA MALAT1) plays its regulative role through Hippo-YAP signaling pathway by targeting miR-181a-5p. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was used to detect the LncRNA MALAT1/miR-181a-5p expression and improve the transfection efficiency. Western blot analysis was used to analyze the expression of proliferation and apoptosis related proteins and Hippo-Yes-associated protein (YAP) signaling pathway related proteins. Cell proliferative ability and cell apoptosis were respectively determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. ELISA assay was for the determination of adherence factors. Immunohistochemistry was to detect the expression of proliferation and adhesion related proteins. LncRNA MALAT1 targeting gene was determined by Dual-luciferase reporter assay. LncRNA MALAT1 was increased in MM cells and LncRNA MALAT1 interference could inhibit cell proliferation and promote cell apoptosis with the changes in the related proteins. Also, LncRNA MALAT1 interference could inhibit cell adhesion through Hippo-YAP signaling pathway. MiR-181a-5p was demonstrated to be a target of LncRNA MALAT1 and miR-181a-5p overexpression could also regulate the changes in cellular behavior in accordance with the LncRNA MALAT1 interference. In addition, LncRNA MALAT1 interference could decrease the expression of miR-181a-5p and inhibit the growth of tumor. In conclusion, this study showed that LncRNA MALAT1 interference inhibited the proliferation and adhesion of myeloma cells by the up-regulation of miR-181a-5p through activating the Hippo-YAP signaling pathway.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , MicroRNAs/metabolismo , Mieloma Múltiplo/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose/genética , Adesão Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Via de Sinalização Hippo , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , Mieloma Múltiplo/genética , Fosforilação , Proteínas Serina-Treonina Quinases/genética , RNA Longo não Codificante/genética , RNA Interferente Pequeno , Transdução de Sinais/genética , Fatores de Transcrição/química , Fatores de Transcrição/genética , Transplante Heterólogo , Regulação para Cima , Proteínas de Sinalização YAPRESUMO
The main objective of the study is to summarize the clinical characteristics of acquired factor XIII (FXIII) deficiency caused by a spontaneous FXIII inhibitor. Here we report a new case of acquired FXIII deficiency caused by FXIII inhibitor and review the medical literature regarding the characteristics and treatment of this disorder. FXIII deficiency caused by FXIII inhibitors is rare and of uncertain pathogenesis. Experience with therapeutic measures is limited to data from case reports. Immunosuppressive drugs may reduce autoantibodies or inhibit the cell clone generating the antibodies and may have been of benefit in our patient. The impact of such therapy on patient prognosis is incompletely known.
Assuntos
Inibidores Enzimáticos/efeitos adversos , Deficiência do Fator XIII/induzido quimicamente , Deficiência do Fator XIII/tratamento farmacológico , Hematoma/induzido quimicamente , Hematoma/tratamento farmacológico , Idoso , Autoanticorpos/efeitos dos fármacos , Azatioprina/uso terapêutico , Inibidores Enzimáticos/administração & dosagem , Fator XIII/metabolismo , Deficiência do Fator XIII/sangue , Deficiência do Fator XIII/imunologia , Hematoma/sangue , Hematoma/imunologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Prednisona/uso terapêuticoRESUMO
This is a retrospective study on six multiple myeloma patients with upfront coagulopathy and bleeding. A detailed description and analysis of clinical characteristics, coagulation factor deficiencies, treatments and outcome of those six multiple myeloma patients are presented. All six patients presented with significant bleeding. One patient was detected with single factor X deficiency and another with single factor VII (FVII) deficiency, whereas four other patients had complex factor deficiencies. The time from symptom presentation to diagnosis ranged from 3 to 10 months. After correct diagnosis and coagulation factor supplementation, those patients were treated with bortezomib/adriamycin/dexamethasone (PAD) or melphalan/dexamethasone/thalidomide (MTD) regimen. It took 29-71 days (median time 46 days) to completely correct coagulation factor deficiencies since the start of therapy for multiple myeloma. Multiple myeloma patients with acquired bleeding disorders may present with large, deep and multiple sites of haematoma or other types of significant bleeding, which may affect bone marrow examination in some of the cases. Patients may be easily misdiagnosed. The routine examinations of erythrocyte sedimentation rate, serum immunoglobulins and blood urine light chain are the key to diagnosis, hence requiring the treating physician to think broadly and look for traits suggesting myeloma as the underlying cause.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Transtornos de Proteínas de Coagulação/complicações , Hematoma/complicações , Hematúria/complicações , Mieloma Múltiplo/complicações , Adulto , Idoso , Sedimentação Sanguínea , Ácidos Borônicos/administração & dosagem , Bortezomib , Coagulantes/uso terapêutico , Transtornos de Proteínas de Coagulação/sangue , Transtornos de Proteínas de Coagulação/diagnóstico , Transtornos de Proteínas de Coagulação/tratamento farmacológico , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Hematoma/sangue , Hematoma/diagnóstico , Hematoma/tratamento farmacológico , Hematúria/sangue , Hematúria/diagnóstico , Hematúria/tratamento farmacológico , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Pirazinas/administração & dosagem , Estudos Retrospectivos , Talidomida/administração & dosagemRESUMO
St. Louis encephalitis virus (SLEV; Flaviviridae, flavivirus) was the major cause of epidemic flaviviral encephalitis in the U.S. prior to the introduction of West Nile virus (WNV) in 1999. However, outbreaks of SLEV have been significantly more limited then WNV in terms of levels of activity and geographic dispersal. One possible explanation for these variable levels of activity is that differences in the potential for each virus to adapt to its host cycle exist. The need for arboviruses to replicate in disparate hosts is thought to result in constraints on both evolution and host-specific adaptation. If cycling is the cause of genetic stability observed in nature and arboviruses lack host specialization, then sequential passage should result in both the accumulation of mutations and specialized viruses better suited for replication in that host. Previous studies suggest that WNV and SLEV differ in capacity for both genetic change and host specialization, and in the costs each accrues from specializing. In an attempt to clarify how selective pressures contribute to epidemiological patterns of WNV and SLEV, we evaluated mutant spectra size, consensus genetic change, and phenotypic changes for SLEV in vivo following 20 sequential passages via inoculation in either Culex pipiens mosquitoes or chickens. Results demonstrate that the capacity for genetic change is large for SLEV and that the size of the mutant spectrum is host-dependent using our passage methodology. Despite this, a general lack of consensus change resulted from passage in either host, a result that contrasts with the idea that constraints on evolution in nature result from host cycling alone. Results also suggest that a high level of adaptation to both hosts already exists, despite host cycling. A strain significantly more infectious in chickens did emerge from one lineage of chicken passage, yet other lineages and all mosquito passage strains did not display measurable host-specific fitness gains. In addition, increased infectivity in chickens did not decrease infectivity in mosquitoes, which further contrasts the concept of fitness trade-offs for arboviruses.
Assuntos
Vírus da Encefalite de St. Louis/metabolismo , Encefalite de St. Louis/transmissão , Animais , Evolução Biológica , Galinhas , Chlorocebus aethiops , Clonagem Molecular , Culicidae , Encefalite de St. Louis/veterinária , Feminino , Variação Genética , Concentração Inibidora 50 , Cinética , Análise de Sequência de DNA , Especificidade da Espécie , Células VeroRESUMO
West Nile virus (WNV), a mosquito-borne flavivirus, has significantly expanded its geographical and host range since its 1999 introduction into North America. The underlying mechanisms of evolution of WNV and other arboviruses are still poorly understood. Studies evaluating virus adaptation and fitness in relevant in vivo systems are largely lacking. In order to evaluate the capacity for host-specific adaptation and the genetic correlates of adaptation in vivo, this study measured phenotypic and genotypic changes in WNV resulting from passage in Culex pipiens mosquitoes. An increase in replicative ability of WNV in C. pipiens was attained for the two lineages of WNV tested. This adaptation for replication in mosquitoes did not result in a replicative cost in chickens, but did decrease cell-to-cell spread of virus in vertebrate cell culture. Genetic analyses of one mosquito-adapted lineage revealed a total of nine consensus nucleotide substitutions with no accumulation of a significant mutant spectrum. These results differed significantly from previous in vitro studies. When St Louis encephalitis virus (SLEV), a closely related flavivirus, was passaged in C. pipiens, moderately attenuated growth in C. pipiens was observed for two lineages tested. These results suggest that significant differences in the capacity for mosquito adaptation may exist between WNV and SLEV, and demonstrate that further comparative studies in relevant in vivo systems will help elucidate the still largely unknown mechanisms of arboviral adaptation in ecologically relevant hosts.
Assuntos
Culex/virologia , Interações Hospedeiro-Patógeno , Vírus do Nilo Ocidental/crescimento & desenvolvimento , Vírus do Nilo Ocidental/genética , Adaptação Biológica , Substituição de Aminoácidos/genética , Animais , Galinhas/virologia , Chlorocebus aethiops , Análise Mutacional de DNA , Evolução Molecular , Mutação de Sentido Incorreto , RNA Viral/genética , Inoculações Seriadas , Células Vero , Ensaio de Placa Viral , Replicação ViralRESUMO
To determine if West Nile virus (WNV) infection of insect cells induces a protective RNAi response, Drosophila melanogaster S2 and Aedes albopictus C6/36 cells were infected with WNV, and the production of WNV-homologous small RNAs was assayed as an indicator of RNAi induction. A distinct population of approximately 25 nt WNV-homologous small RNAs was detected in infected S2 cells but not C6/36 cells. RNAi knockdown of Argonaute 2 in S2 cells resulted in slightly increased susceptibility to WNV infection, suggesting that some WNV-homologous small RNAs produced in infected S2 cells are functional small interfering RNAs. WNV was shown to infect adult D. melanogaster, and adult flies containing mutations in each of four different RNAi genes (Argonaute 2, spindle-E, piwi, and Dicer-2) were significantly more susceptible to WNV infection than wildtype flies. These results combined with the analysis of WNV infection of S2 and C6/36 cells support the conclusion that WNV infection of D. melanogaster, but perhaps not Ae. albopictus, induces a protective RNAi response.
Assuntos
Drosophila melanogaster/genética , Drosophila melanogaster/virologia , Interferência de RNA , Vírus do Nilo Ocidental/patogenicidade , Adenosina Trifosfatases/genética , Aedes/genética , Aedes/virologia , Animais , Proteínas Argonautas , Sequência de Bases , Linhagem Celular , Chlorocebus aethiops , Culex/genética , Culex/virologia , Primers do DNA/genética , Proteínas de Drosophila/genética , Feminino , Genes de Insetos , Mutação , Proteínas/genética , RNA Helicases/genética , Complexo de Inativação Induzido por RNA/genética , Ribonuclease III , Especificidade da Espécie , Células VeroRESUMO
A small-plaque variant (SP) of West Nile virus (WNV) was isolated in Vero cell culture from kidney tissue of an American crow collected in New York in 2000. The in vitro growth of the SP and parental (WT) strains was characterized in mammalian (Vero), avian (DF-1 and PDE), and mosquito (C6/36) cells. The SP variant replicated less efficiently than did the WT in Vero cells. In avian cells, SP growth was severely restricted at high temperatures, suggesting that the variant is temperature sensitive. In mosquito cells, growth of SP and WT was similar, but in vivo in Culex pipiens (L.) there were substantial differences. Relative to WT, SP exhibited reduced replication following intrathoracic inoculation and lower infection, dissemination, and transmission rates following oral infection. Analysis of the full length sequence of the SP variant identified sequence differences which led to only two amino acid substitutions relative to WT, prM P54S and NS2A V61A.
Assuntos
Variação Genética , Replicação Viral/fisiologia , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/genética , Aedes/virologia , Animais , Doenças das Aves/virologia , Chlorocebus aethiops , Corvos/virologia , Insetos Vetores/fisiologia , Insetos Vetores/virologia , New York/epidemiologia , Temperatura , Células Vero , Febre do Nilo Ocidental/epidemiologia , Vírus do Nilo Ocidental/classificação , Vírus do Nilo Ocidental/fisiologiaRESUMO
Inactivated whole avian influenza virus (AIV) vaccine provides protection against homologous haemagglutinin (HA) subtype virus, but poor protection against a heterologous HA virus. Moreover, it induces chickens to produce antibodies to cross-reactive antigens, especially nucleoprotein, which is limits AIV serological surveillance. In this study, a recombinant fowlpox virus co-expressing HA (H5 subtype) and NA (NI subtype)genes of AIV was evaluated for its ability to protect chickens against intramuscular challenge with a lethal dose of highly pathogenic (HP) AIV. Susceptible chickens were also vaccinated by wing-web puncture with the parent fowlpox vaccine virus. Following challenge 4 weeks later with HPAIV, all chickens vaccinated with recombinant virus were protected, while the chickens vaccinated with either the unaltered parent fowlpox vaccine virus or unvaccinated controls experienced 100% mortality following challenge. This protection was accompanied by the high levels of specific antibody to the respective components of the recombinant vaccine. The above results showed that rFPV-HA-NA could be a potential vaccine to replace current inactivated vaccines for preventing AI.