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This study focuses on acute myeloid leukemia (AML), a condition with a 5-year survival rate below 30% despite various treatment options. Recent strides in targeted therapies have shown promise, leading to better outcomes with minimal toxicity. These advances underscore the importance of discovering new diagnostic and prognostic targets for AML. In this context, the authors investigated the expression of microRNA-106b-5p (miR-106b-5p), Rab10 mRNA, and Rab10 proteins in peripheral blood and bone marrow (BM) samples from both healthy individuals and AML patients at different stages of the disease (initial diagnosis, recurrence, and complete remission). This examination aimed to identify potential biomarkers for AML diagnosis, treatment, and prognosis. From June 2021 to December 2022, they collected 100 BM and peripheral blood samples. The relative expression of miR-106b-5p and Rab10 mRNA in the BM of AML patients was measured using Real-time polymerase chain reaction (qRT-PCR), while the relative expression of Rab10 protein in serum was determined using the ELISA method. The chromosomal karyotype of initially diagnosed patients was analyzed using the R tape. The qRT-PCR results revealed that the expression of miR-106b-5p and Rab10 mRNA were significantly higher in patients at initial diagnosis and recurrence compared with healthy individuals and those in complete remission (p < 0.001). They observed a significant reduction in the expression of miR-106b-5p, Rab10 mRNA, and Rab10 protein in the BM and peripheral blood of patients during complete remission (p < 0.05), as demonstrated by dynamic monitoring of five patients in the initial group. Furthermore, they found a close association between the expression of miR-106b-5p and the number of white blood cells at the initial diagnosis in AML patients (p < 0.05). Spearman correlation analysis revealed a positive correlation among miR-106b-5p, Rab10 mRNA, and Rab10 proteins (p < 0.05). The diagnostic potential of miR-106b-5p and Rab10 proteins was underscored by Receiver Operating Characteristic (ROC) curve analysis, which demonstrated their high accuracy in AML diagnosis (AUC: 0.944 and 0.853, respectively; p < 0.0001). Additionally, Kaplan-Meier survival analysis suggested that lower expression of these markers was associated with better prognoses (p < 0.05). In summary, their findings propose miR-106b-5p and Rab10 proteins as promising biomarkers for AML, offering insights for diagnosis, treatment, and prognosis.
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MicroRNAs (miRNAs) are a group of noncoding RNAs that exert master regulatory functions in post-transcriptional gene expression. Accumulating evidence shows that miRNAs can either promote or suppress tumorigenesis by regulating different target genes or pathways and may be involved in the occurrence of carcinoma. miR4093p is dysregulated in a variety of malignant cancers. It plays a fundamental role in numerous cellular biological processes, such as cell proliferation, apoptosis, migration, invasion, autophagy, angiogenesis and glycolysis. In addition, studies have shown that miR4093p is expected to become a noninvasive biomarker. Identifying the molecular mechanisms underlying miR4093pmediated tumor progression will help investigate miR4093pbased targeted therapy for human cancers. The present review comprehensively summarized the recently published literature on miR4093p, with a focus on the regulation and function of miR4093p in various types of cancer, and discussed the clinical implications of miR4093p, providing new insight for the diagnosis and treatment of cancers.
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Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , MicroARNs , Neoplasias , Humanos , MicroARNs/genética , Neoplasias/genética , Neoplasias/patología , Neoplasias/terapia , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular/genética , Terapia Molecular Dirigida/métodos , Apoptosis/genética , Movimiento Celular/genéticaRESUMEN
Acute myeloid leukemia cytogenetics and molecular subtypes are connected with microRNAs, although it is unclear how miRNAs affect AML pathogenesis. miR-409-3p expression is downregulated in bone marrows, as we have previously demonstrated in our team. Nevertheless, the tumor-suppressing activities and molecular mechanisms of miR-409-3p remain unknown. Hence, in this study, we investigate at the functional significance of miR-409-3p in the development of AML. We found that a significant decrease in miR-409-3p expression was observed in THP-1 cell. The expression of miR-409-3p was altered in THP-1 by transfecting with agomiR-409-3p and agomiR-409-3p NC. A series of experiments showed that overexpression of miR-409-3p expression significantly suppressed proliferation and increased the apoptosis of THP-1. Moreover, Rab10 was confirmed as a direct target gene of miR-409-3p and was negatively modulated by miR-409-3p. Rab10 downregulation imitated the suppressed proliferation and increased the apoptosis of THP-1. Furthermore, miR-409-3p overexpression or Rab10 knockdown obviously down-regulated the expression levels of Bcl-2, but up-regulated Bax expression. In a xenograft mouse model, miR-409-3p-overexpressed THP-1 cells resulted in much less tumor weight and size in the mice bearing the cells as compared to the mock-transfected mice. Collectively, our findings demonstrated that miR-409-3p exerted tumor suppressor gene effects in AML by directly targeting Rab10, which might provide a promising therapeutic target for AML.
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Leucemia Mieloide Aguda , MicroARNs , Humanos , Animales , Ratones , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Leucemia Mieloide Aguda/patología , Médula Ósea/patología , Apoptosis/genética , Línea Celular Tumoral , Proteínas de Unión al GTP rab/genética , Proteínas de Unión al GTP rab/metabolismoRESUMEN
miRNAs are a type of small endogenous noncoding RNA composed of 20-22 nucleotides that can regulate gene expression by targeting the 3' untranslated region of mRNA. Many investigations have discovered that miRNAs have a role in the development and progression of human cancer. Several aspects of tumor development are affected by miR-425, including growth, apoptosis, invasion, migration, epithelial-mesenchymal transition, and drug resistance. In this article, we discuss the properties and research development of miR-425, focusing on the regulation and function of miR-425 in various cancers. Furthermore, we discuss the clinical implications of miR-425. This review may broaden our horizon for better understanding the role of miR-425 as biomarkers and therapeutic targets in human cancer.
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MicroARNs , Neoplasias , Humanos , Movimiento Celular/genética , Neoplasias/patología , MicroARNs/genética , MicroARNs/metabolismo , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica/genética , Línea Celular Tumoral , Proliferación Celular , Regiones no Traducidas 3'RESUMEN
MicroRNA are non-coding small RNAs that bind to their target mRNA and cause mRNA degradation or translation inhibition. MiRNA dysregulation is linked to a variety of human cancers and has a role in the genesis and development of cancer pathology. MiR-328 has been reported to be involved in various human cancers. And miR-328 is considered a key regulator in human cancer. It participates in biological processes such as proliferation, apoptosis, invasion, migration, and EMT. The present review will combine the basic and clinical studies to find that miR-328 promotes tumorigenesis and metastasis in human cancer. And we will describe the diagnostic, prognostic, and therapeutic value of miR-328 in various human cancers.
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MicroARNs , Neoplasias , Humanos , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Proliferación Celular/genética , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/diagnóstico , Neoplasias/genéticaRESUMEN
Human is the host of the Epstein-Barr virus (EBV) especially in childhood and adolescence. Most of them are asymptomatic infection and self-limiting. However, for those patients who suffer from immune dysfunction, EBV infection will be life-threatening. Epstein-Barr virus-associated hemophagocytic lymphohistocytosis (EBV-HLH) is one of the severe effects. The diagnosis and differential diagnosis of EBV-HLH and other EBV infectious diseases are mentioned in this paper. The molecular biology mechanism and complications of EBV-HLH are equally briefly presented. It also provides a practical method for the genetic diagnosis of such diseases and the differential diagnosis with other human immunodeficiency diseases for medical scientists in routine clinical practice.
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Susceptibilidad a Enfermedades , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/fisiología , Interacciones Huésped-Patógeno , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/etiología , Biomarcadores , Biopsia , Médula Ósea/patología , Examen de la Médula Ósea , Análisis Citogenético , Diagnóstico Diferencial , Manejo de la Enfermedad , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/terapia , MicroARNs/genética , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: MicroRNA-409-3p, is down-regulated in a variety of malignant diseases. However, the expression level and clinical value of microRNA-409-3p in acute myeloid leukemia has not yet been systematically studied. METHODS: We collected 88 bone marrow samples derived from 73 patients with acute myeloid leukemia and 15 healthy controls. Then we evaluated the expression of microRNA-409-3p by quantitative real-time PCR. RESULTS: The results revealed that compared with the healthy controls, microRNA-409-3p expression in a newly diagnosed group was significantly lower (p < 0.001). In addition, the microRNA-409-3p expression in the complete remission group was strikingly higher compared to that of the newly diagnosed group (p < 0.001). There was a correlation between microRNA-409-3p expression and white blood cells (p = 0.021). Most importantly, the micro-RNA-409-3p low expression group indicated a shorter event-free survival compared with microRNA-409-3p high expression group by using Kaplan-Meier analysis (p < 0.0438). CONCLUSIONS: The microRNA-409-3p expression level could be a novel potential biomarker for acute myeloid leukemia diagnosis and prognosis, providing a new therapeutic strategy for acute myeloid leukemia treatment.
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Examen de la Médula Ósea/métodos , Leucemia Mieloide Aguda , MicroARNs/metabolismo , Biomarcadores de Tumor/metabolismo , Regulación hacia Abajo , Femenino , Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
MicroRNAs are a class of small non-coding RNAs that are 19-22 nucleotides in length and regulate a variety of biological processes at the post-transcriptional level. MicroRNA dysregulation disrupts normal biological processes, resulting in tumorigenesis. Acute myeloid leukemia is an invasive hematological malignancy characterized by the abnormal proliferation and differentiation of immature myeloid cells. Due to the low 5-year survival rate, there is an urgent need to discover novel diagnostic markers and therapeutic targets. In recent years, microRNAs have been shown to play important roles in hematological malignancies by acting as tumor suppressors and oncogenes. MicroRNAs have the potential to be a breakthrough in the diagnosis and treatment of acute myeloid leukemia. In this review, we summarize the biology of microRNAs and discuss the relationships between microRNA dysregulation and acute myeloid leukemia in the following aspects: signaling pathways, the abnormal biological behavior of acute myeloid leukemia cells, the clinical application of microRNAs and competing endogenous RNA regulatory networks.
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Carcinogénesis/metabolismo , Regulación Leucémica de la Expresión Génica , Neoplasias Hematológicas/metabolismo , Leucemia Mieloide Aguda/metabolismo , MicroARNs/metabolismo , ARN Neoplásico/metabolismo , Carcinogénesis/patología , Diferenciación Celular , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Transducción de SeñalRESUMEN
BACKGROUND: Idiopathic infantile nystagmus (IIN) is a high genetically heterogeneous ophthalmic disease and is often associated with pathogenic mutations in FRMD7 and GPR143, respectively. Idiopathic infantile nystagmus manifests as involuntary periodic rhythmic oscillation of the eyes in the very early life, which decreases visual acuity and affects the quality of life. OBJECTIVE AND METHODS: The aim of our study was to reveal a possible pathogenic variant through the investigation of a Chinese Han family with IIN with an implementation of a next-generation sequencing method. Isolated DNA analysis was followed by Sanger sequencing validation. We also performed the detailed ophthalmological examination of family members. RESULTS: We identified a novel frameshift variant in FRMD7 (NM_194277.2: c.1419_1422dup, p.Tyr475fs), which leads to a frameshift mutation since tyrosine (Tyr) at 475 codon of FRMD7 protein (p.Tyr475fs) and co-segregates with IIN phenotype in this family. CONCLUSIONS: We found a novel frameshift FRMD7 variant in a Chinese Han family, which may be causative variant for IIN and can further enrich the mutation spectrum and uncover the etiology of IIN.
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Pueblo Asiatico/genética , Proteínas del Citoesqueleto/genética , Mutación del Sistema de Lectura/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de la Membrana/genética , Nistagmo Congénito/genética , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Proteínas del Citoesqueleto/química , Familia , Femenino , Humanos , Masculino , Proteínas de la Membrana/química , LinajeRESUMEN
Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by repetitive motor movements and vocal tics. The clinical manifestations of TS are complex and often overlap with other neuropsychiatric disorders. TS is highly heritable; however, the underlying genetic basis and molecular and neuronal mechanisms of TS remain largely unknown. We performed whole-exome sequencing of a hundred trios (probands and their parents) with detailed records of their clinical presentations and identified a risk gene, ASH1L, that was both de novo mutated and associated with TS based on a transmission disequilibrium test. As a replication, we performed follow-up targeted sequencing of ASH1L in additional 524 unrelated TS samples and replicated the association (P value = 0.001). The point mutations in ASH1L cause defects in its enzymatic activity. Therefore, we established a transgenic mouse line and performed an array of anatomical, behavioral, and functional assays to investigate ASH1L function. The Ash1l+/- mice manifested tic-like behaviors and compulsive behaviors that could be rescued by the tic-relieving drug haloperidol. We also found that Ash1l disruption leads to hyper-activation and elevated dopamine-releasing events in the dorsal striatum, all of which could explain the neural mechanisms for the behavioral abnormalities in mice. Taken together, our results provide compelling evidence that ASH1L is a TS risk gene.
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Proteínas de Unión al ADN/genética , N-Metiltransferasa de Histona-Lisina/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Animales , Niño , Preescolar , China , Proteínas de Unión al ADN/metabolismo , Familia , Femenino , Predisposición Genética a la Enfermedad/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Mutación/genética , Padres , Trastornos de Tic/genética , Síndrome de Tourette/complicaciones , Factores de Transcripción/genética , Secuenciación del Exoma/métodosRESUMEN
Hyperuricemia (HUA) in women with preeclampsia (PE) not only indicates a reminder of severity but also contributes directly to the pathogenesis of PE. ATP-binding cassette subfamily G member 2 (ABCG2) has a very strong effect on the serum urate concentrations. Our aim was to investigate the association between polymorphisms of ABCG2 with PE in Chinese Han female population. A cohort of 793 preeclamptic women (466 PE with HUA and 327 PE without HUA) and 744 normal pregnant women recruited in this study were genotyped for genetic distribution of Q141K (rs2231142) and Q126X (72552713) in ABCG2 by the TaqMan allelic discrimination real-time PCR. There was no statistically significant difference of genotypic and allelic frequencies between PE and the normal pregnant women in Q141K (Χ2â¯=â¯1.11, Pâ¯=â¯0.58 by genotype; Χ2â¯=â¯0.32, Pâ¯=â¯0.57 by allele) and Q126X (Pâ¯=â¯0.33 by genotype; Pâ¯=â¯0.33 by allele), and no significant difference was found in the genetic distribution of Q141K and Q126X between PE with HUA, PE without HUA and controls. Additionally, this study observed no significant difference in genotypic and allelic distribution between early/late-onset PE with/without HUA or mild/severe PE with/without HUA and control subgroups. Based on our findings, the ABCG2 Q141K and Q126X polymorphisms may not be associated with PE in Chinese Han women.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Predisposición Genética a la Enfermedad , Proteínas de Neoplasias/genética , Preeclampsia/genética , Adulto , Pueblo Asiatico , Estudios de Casos y Controles , China , Estudios de Cohortes , Femenino , Genotipo , Humanos , EmbarazoRESUMEN
OBJECTIVES: Hereditary spherocytosis (HS) is a genetic heterogeneous disorder characterized by sphere-shaped erythrocytes on peripheral blood smear with a few clinical manifestations. As an important red cell membrane protein, ankyrin 1 can interact with transmembrane proteins and the membrane skeleton and mutations in the ankyrin 1 (ANK1) genes affect about half of all patients with HS. The purpose of this study was to investigate a Chinese Han family with HS to find out the causative gene mutation and explore the genotype-phenotype correlation which can provide the basis for the pathogenesis and prenatal diagnosis for this disease. METHODS: Whole exome sequencing (WES) followed by Sanger sequencing was performed on subjects with HS from a Chinese family in Shandong Province. RESULTS: A de novo nonsense ANK1 mutation (c.796G > T, p.Glu266X), a single-nucleotide change from G to T which caused a substitution from glutamic acid to an immature stop codon at codon 266, was identified. DISCUSSION: Our finding suggested that a de novo nonsense mutation in ANK1 may be causative to HS which plays an important role in supplementing the mutational spectrum of the ANK1 and explaining the mechanism of HS. Our study also indicated that WES can be an effective and accurate diagnostic tool in the discovery of causative mutations in genetic heterogeneous Mendelian disorders.
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Ancirinas/genética , Mutación , Esferocitosis Hereditaria/sangre , Esferocitosis Hereditaria/genética , Alelos , Biomarcadores , Niño , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Fenotipo , Polimorfismo de Nucleótido Simple , Reproducibilidad de los Resultados , Análisis de Secuencia de ADN , Esferocitosis Hereditaria/diagnóstico , Secuenciación del ExomaRESUMEN
The clinical significance of the dominant-negative Ikaros 6 (DN-IK6) in the treatment of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+-ALL) with tyrosine kinase inhibitors (TKIs) remains elusive. In the present study, it was demonstrated that DN-IK6 was overexpressed in B-cell (B)-ALL cases compared with T cell-ALL cases at the mRNA and protein levels. Furthermore, nucleotide sequencing revealed that DN-IK6 was due to the deletion of IKAROS family zinc finger 1 exons 4-7. The outcome of patients with Ph+-B-ALL with DN-IK6, and treated with TKIs and hyper-cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen were restrospectively evaluated in a 2 year follow-up. The results demonstrated that those with the DN isoform exhibited significantly lower incidences of remission, shorter median cumulative incidence of relapse times (P<0.05) and shorter median overall survival times (P<0.05) compared with those without the DN isoform. In conclusion, the results of the present study demonstrated that DN-IK6 is overexpressed in the majority of patients with Ph+-ALL, and is significantly associated with resistance to TKI therapy.
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OBJECTIVE: To explore the expression of focal adhesion kinase (FAK) in patients with acute leukemia (AL) and its clinical significance. METHODS: The FAK mRNA levels in leukemic cells of 50 patients with AL and bone marrow mononuclear cells(BMMNC) of 10 healthy controls were measured by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The bone marrow cell chromosomes were prepared using direct and short term culture, and karyotyping was performed by R-banding technique. RESULTS: The expression positive rate of FAK mRNA in leukemic cells of 50 patients with AL was 66.0%, which was significantly higher than that in normal controls (20.0%) (P<0.05). The expression positive rates and levels of FAK mRNA in both ALL and ANLL cells were statistically significantly higher than those in normal controls (P<0.05), but the difference between ALL and ANLL cells was not significant (P>0.05). All the expression- positive rates and levels of FAK mRNA in newly diagnosed AL patients and the relapsed AL patients were significantly higher than those in normal controls (P<0.05), but the difference between the newly diagnosed AL patients and the relapsed AL patients was not significant (P>0.05). Morecover, the expression plsitive rate and levels of FAK mRNA in the remitted patients were lower than those in newly diagnosed and relapsed patients (P<0.05), but were no statistically significantly different from normal controls (P>0.05). The expression- positive rate and level of FAK mRNA in the AL patients with abnormal karyotype were significantly higher than those in the AL patients without abnormal karyotype (P<0.05). CONCLUSION: FAK mRNA over-express in the leukemia patients, which may be related with the outome of disease, possibly providing novel targeting sites for the treatment of leukemia.
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Quinasa 1 de Adhesión Focal/metabolismo , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Leucemia Mieloide Aguda/metabolismo , Enfermedad Aguda , Células de la Médula Ósea/metabolismo , Humanos , Leucemia , Leucemia Mieloide Aguda/patología , ARN MensajeroRESUMEN
Although Tourette syndrome (TS) is a chronic neuropsychiatric disorder whose pathogenesis remains unclear, genetic factors play an important role in the occurrence and development. A variety of studies have been shown that the candidate genes related to cholinergic neurons may be associated with the onset of TS. To investigate the association between the SLC5A7 polymorphisms and Tourette syndrome (TS) in the Chinese Han population, the SNP rs1013940, rs2433718, and rs4676169 were genotyped in 401 TS trios and 400 controls. The transmission disequilibrium test (TDT) and haplotype relative risk (HRR) compared genetic distributions of trios, while the chi-square test compared patients and controls. However, no transmission disequilibrium was found between the three SLC5A7 SNPs and TS. Therefore, we think that this gene may not be the main risk factor on the onset of TS. However, these results should be further validated in different populations.
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Predisposición Genética a la Enfermedad , Desequilibrio de Ligamiento/genética , Simportadores/genética , Síndrome de Tourette/genética , Adolescente , Pueblo Asiatico/genética , Niño , Preescolar , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Philadelphia chromosome-positive acute myeloid leukemia is controversial and difficult to distinguish from the blast phase of chronic myeloid leukemia. As a myeloid neoplasm, rare cases of this leukemia manifest multiple soft-tissue tumors or bone lytic lesions. In this paper, we describe a 49-year-old male patient who had an abrupt onset with sharp chest pain, fever, fatigue, emaciation, and splenomegaly. 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) result showed diffuse and uneven hypermetabolic lesions in the bone marrow with peripheral bone marrow expansion, multiple soft tissue neoplasms with high 18F-FDG uptake, and lytic bone lesions. Bone marrow smear and biopsy detected aberrant blast cells expressing myeloid rather than lymphoid immunophenotype marker. For the existence of Philadelphia chromosome and BCR-ABL1 fusion gene together with complex chromosome abnormalities, a diagnosis of Philadelphia-positive acute myeloid leukemia was made, although the type (de novo or blast crisis) remained unclear.
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Médula Ósea/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico por imagen , Leucemia Mieloide Aguda/diagnóstico por imagen , Osteólisis/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
Infection with Epstein-Barr virus (EBV) may be correlated to the onset of acute leukemia (AL). Studies were performed to investigate the relationship between EBV infection and immunophenotyping of acute lymphoblastic leukemia (ALL) and chromosome aberrations. Additionally, the effects of EBV on clinical prognosis were described. Fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect EBV-DNA copy numbers from bone marrow in 110 cases of patients with ALL, 75 cases of patients with acute myeloid leukemia (AML), and 37 cases of hematologically healthy control subjects. EBV-DNA copies were found in 64 of 185 (34.6%) patients with AL and 2 of 37 healthy control subjects (P < 0.001). The EBV infection rate of ALL patients, AML patients, and healthy controls was 40.9% (45/110), 25.3% (19/75), and 5.4% (2/37), respectively. The positive rate of EBV in the ALL and AML groups was higher than in healthy subjects (P < 0.05). EBV-DNA copies were found in 1 of 12 (8.3%) T-ALLs and 44 of 98 (44.9%) B-ALLs, the positive rate of EBV in B-ALLs increased significantly compared to the rate of T-ALLs (P < 0.05). Chromosome karyotype analysis showed that EBV infection rates in B-ALL, T-ALL, and AML patients with chromosome abnormalities were 46.3% (25/54), 33.3% (1/3), and 30% (9/30), respectively. There was no statistical significance between chromosome abnormality and EBV infection (P > 0.05). In addition, EBV+ -ALLs had higher relapse and mortality rates than that of EBV- -ALLs. Together, we conclude that EBV infection may be correlated with the incidence of AL, and the infection rate of EBV in B-ALL was higher than that of T-ALL. EBV-positive patients showed an unfavorable prognosis.
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Aberraciones Cromosómicas , Infecciones por Virus de Epstein-Barr/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/virología , Niño , Preescolar , ADN Viral/análisis , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Carga Viral , Adulto JovenRESUMEN
Alpha-melanocyte-stimulating hormone (α-MSH) is processed from proopiomelanocortin (POMC) and acts on the melanocortin receptors, MC3 and MC4. α-MSH plays a key role in energy homeostasis. In the present study, to shed light on the mechanisms by which α-MSH exerts its anorectic effects, extracellular neuronal activity was recorded in the hypothalamus and the dorsal vagal complex (DVC) of anesthetized rats. We examined the impact of α-MSH on glucose-sensing neurons and gastric distension (GD) sensitive neurons. In the lateral hypothalamus (LHA), α-MSH inhibited 75.0% of the glucose-inhibited (GI) neurons. In the ventromedial nucleus (VMN), most glucose-sensitive neurons were glucose-excited (GE) neurons, which were mainly activated by α-MSH. In the paraventricular nucleus (PVN), α-MSH suppressed the majority of GI neurons and excited most GE neurons. In the DVC, among the 20 GI neurons examined for a response to α-MSH, 1 was activated, 16 were depressed, and 3 failed to respond. Nineteen of 24 GE neurons were activated by α-MSH administration. Additionally, among the 42 DVC neurons examined for responses to GD, 23 were excited (GD-EXC) and 19 were inhibited (GD-INH). Fifteen of 20 GD-EXC neurons were excited, whereas 11 out of 14 GD-INH neurons were suppressed by α-MSH. All these responses were abolished by pretreatment with the MC3/4R antagonist, SHU9119. In conclusion, the activity of glucose-sensitive neurons and GD-sensitive neurons in the hypothalamus and DVC can be modulated by α-MSH.
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Hipotálamo/fisiología , Neuronas/fisiología , Transmisión Sináptica/efectos de los fármacos , Nervio Vago/fisiología , alfa-MSH/farmacología , Animales , Femenino , Masculino , Ratas , Ratas Wistar , Transmisión Sináptica/fisiologíaRESUMEN
The hypoxia-inducible factor (HIF) is recognized as the master regulator of hypoxia response. HIF-α subunits expression are tightly regulated. In this study, our data show that ts20 cells still expressed detectable E1 protein even at 39.5° C for 12 h, and complete depletion of E1 protein expression at 39.5° C by siRNA enhanced HIF-1α and P53 protein expression. Further inhibition of E1 at 39.5 °C by siRNA, or E1 inhibitor Ube1-41 completely blocked HIF-1α degradation. Moreover, immunoprecipitations of co-transfection of HA-ubiquitin and FLAG-HIF-1α plasmids directly confirmed the involvement of ubiquitin in the hypoxic degradation of HIF-1α. Additionally, hypoxic HIF-1 α degradation is independent of HAF, RACK1, sumoylation or nuclear/cytoplasmic localization. Taken together, our data suggest that constitutive HIF-1α protein degradation in hypoxia is absolutely ubiquitination-dependent, and unidentified E3 ligase may exist for this degradation pathway.
Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Estrés Oxidativo/fisiología , Oxígeno/metabolismo , Ubiquitina/metabolismo , Ubiquitinación/fisiología , Hipoxia de la Célula/fisiología , Células HeLa , Células Hep G2 , HumanosRESUMEN
Acute promyelocytic leukemia (APL) with variant translocations is rare. The patient of the present case report, a 2-year-old male with a microgranular variant of APL carrying der(17) ins(17;15) translocation, exhibited fever and epistaxis. The complete blood count showed marked leukocytosis with 72% atypical promyelocytes, anemia and thrombocytopenia. Conventional cytogenetic analysis of the bone marrow cells revealed a karyotype of 47, XY, add(3)(q29), -7, ins(17;15)(q12;q14q22),+21,+mar. The promyelocytic leukemia/retinoic acid receptor α (PML/RARα) rearrangement and insertion were confirmed by fluorescence in situ hybridization. The PML/RARα transcripts were not detected by the reverse transcription polymerase chain reaction, and the patient was diagnosed with microgranular variant M3 APL. The patient achieved remission after a 30-day treatment and was still in remission during a recent follow-up. The present findings suggest that the ins(17;15) variant in APL may not be associated with an unfavorable prognosis. In summary, we reported an extremely rare case of APL with der(17) ins(17;15) abnormality in a pediatric patient and reviewed the literature.