RESUMO
Circular RNAs (circRNAs), a type of endogenous noncoding RNA (ncRNA), exert vital roles in leukemia progression and are promising prognostic factors. Here, we report a novel circRNA, circSLC25A13 (hsa_circ_0081188), which was increased in acute myeloid leukemia (AML) patients with poor overall survival (OS) comparing to patients with good prognosis. Knockdown of circSLC25A13 in AML cells inhibited proliferation and increased cell apoptosis in vitro and in vivo. Enhanced circSLC25A13 expression promoted the survival of AML cells. Mechanistically, circSLC25A13 played as a microRNA sponge of miR-616-3p, which inhibited the expression of adenylate cyclase 2 (ADCY2). Downregulation of miR-616-3p and overexpression of ADCY2 partially rescued circSLC25A13 deficient induced cell growth arrest. In summary, through competitive absorption of miR-616-3p and thereby upregulating ADCY2 expression, circSLC25A13 promoted AML progression. Moreover, circSLC25A13 may represent a potential novel biomarker for the prognosis of AML and offer a potential therapeutic target for AML treatment.
Assuntos
Leucemia Mieloide Aguda , MicroRNAs , Humanos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genéticaRESUMO
Minimal residual disease (MRD) is an important independent prognostic factor for relapse and survival in acute lymphoblastic leukaemia (ALL). Compared with adult B-cell ALL, reports of adult T-cell ALL (T-ALL) MRD have been scarce and mostly based on molecular methods. We evaluated the prognostic value of multiparameter flow cytometry (FCM)-based MRD at the end of induction (EOI-MRD). The present retrospective study included 94 adult patients with T-ALL. MRD was detected by six- to eight-colour FCM. Patients who were EOI-MRD positive had a higher cumulative incidence of relapse (CIR) (87·6% vs. 38·8%, P = 0·0020), and a lower relapse-free survival (RFS) (5·4% vs. 61·0%, P = 0·0005) and overall survival (OS) (32·7% vs. 69·7%, P < 0·0001) than those who were EOI-MRD negative. Moreover, for patients who received allogeneic haematopoietic stem cell transplantation (allo-HSCT) at their first remission, EOI-MRD positivity was predictive of post-transplant relapse (2-year CIR: 68·2% vs. 4·0%, P = 0·0003). Multivariate analysis showed that EOI-MRD was an independent prognostic factor for CIR [hazard ratio (HR) 2·139, P = 0·046], RFS (HR 2·125, P = 0·048) and OS (HR 2·987, P = 0·017). In conclusion, EOI-MRD based on FCM was an independent prognostic factor for relapse and survival in adult T-ALL. For patients who underwent HSCT, EOI-MRD could be used to identify patients with a high risk of relapse after allo-HSCT.
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Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células T Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Estudos Retrospectivos , Medição de Risco , Taxa de SobrevidaRESUMO
The identification of genetic risk subgroups of T-cell acute lymphoblastic leukemia (T-ALL) may provide evidence for risk stratification and individualized treatment. We investigated the characteristics and prognostic value of tumor suppressor gene CDKN2A deletions in 101 patients with T-ALL. The CDKN2A deletion was present in 23% (23/101) of T-ALL by fluorescence in situ hybridization (FISH). The most common type of CDKN2A deletion was homozygous deletion (70%, 16/23). A lower frequency of CDKN2A deletion was found in patients with early T-cell precursor (ETP) ALL than in patients with non-ETP-ALL (10.4% vs 34.0%; P = .008). Deletion of CDKN2A was significantly associated with younger age (P = .001), higher white blood cell (WBC) count (P < .001) and higher lactate dehydrogenase (LDH) level (P = .002). Patients with CDKN2A deletion had lower 2-year overall survival (OS) and event-free survival (EFS) rates than patients without CDKN2A deletion (2-year OS: 18.6% ± 8.9% vs 47.4% ± 6.2%, P = .032; EFS: 16.4 ± 8.3 vs 38.6 ± 5.9%, P = .022). In multivariable analysis, CDKN2A deletion was an independent adverse prognostic factor for OS (P = .016). In conclusion, adult T-ALL patients with CDKN2A deletion had a poor prognosis, and these patients might benefit from intensive chemotherapy or allogeneic hematopoietic stem-cell transplantation.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/deficiência , Deleção de Genes , Genes p16 , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Adulto , Idoso , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China/epidemiologia , Terapia Combinada , Análise Mutacional de DNA , DNA de Neoplasias/genética , Feminino , Transplante de Células-Tronco Hematopoéticas , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Prognóstico , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To characterize cytogenetic changes and prognosis of patients with acute myeloid leukemia (AML) from different age groups. METHODS: The karyotypes of 515 AML patients were analyzed by using short-term culture of bone marrow cells and R-banding technique. Combined with FAB typing and genetic testing, cytogenetic changes and prognosis of different age groups were analyzed. RESULTS: The abnormal cloning rate was 54.6% among the 515 patients. The abnormal cloning rate and adverse risk karyotype proportion of those with myeloproliferative syndromes (MDS) and secondary AML were higher than those with de novo AML (P = 0.027; P<0.01). A significant difference was found in the number of structural abnormalities and proportion of favorable risk karyotypes among different age groups (P = 0.026; P = 0.004). And there was also a significant difference in the abnormal cloning rate between different FAB types (P<0.01). In those with non-acute promyelocytic leukemia (APL), the expression level of WT1 gene seemed to affect the prognosis. The survival rate of patients with karyotypes of adverse risk was lower than those with karyotypes of favorable risk (P = 0.015). The survival rate of the ≥60-year-old group was lower than the ≤30-year-old and 31 to 59-year-old groups (P<0.01, P<0.01). CONCLUSION: The karyotypes of AML patients have different age distribution characteristics. The survival rate of ≥60-years-old group and karyotype of poor prognosis is low. Patients with MDS with secondary AML have a poor prognosis.
Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adulto , Aberrações Cromossômicas , Análise Citogenética , Citogenética , Humanos , Cariótipo , Cariotipagem , Pessoa de Meia-Idade , PrognósticoRESUMO
Approximately 50% of older patients with acute myeloid leukemia (AML) do not obtain chromosomal abnormalities as an effective risk-stratification, and present cytogenetically normal AML (CN-AML). To develop a reliable prediction model for stratifying the risk of these elderly patients, we conducted a study with a discovery and validation design. As a result, we found the top 6 mutated genes in the discovery cohort of 26 case by the whole exome sequencing, and verified as recurrent mutations in the large cohort of 329 patients by Sanger sequencing. The top 6 genes were NPM1, FLT3-ITD, DNMT3A, CEBPA double allele, IDH1 and IDH2 mutations, and the frequency of each gene in the combining cohort was 36.8%, 19.8%, 20.1%, 5.8%, 14.9% and 22.5%, respectively. In addition, clinical variables such as age, white blood cell counts, genes of IDH1 and DNMT3A mutations, European LeukemiaNet genotype (NPM1 mutations and lacking FLT3-ITD or CEBPA double allele mutations) and treatment protocols were independent factors for predicting the probabilities of overall and event-free survival. The prediction nomograms based on these significant factors showed accurate discrimination. In conclusion, we developed a reliable prediction model for stratifying the risk of elderly patients with CN-AML.
Assuntos
Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Mutação/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Regulação Leucêmica da Expressão Gênica/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Prognóstico , Fatores de Risco , Sequenciamento do Exoma/métodosRESUMO
BACKGROUND: MicroRNAs are of special interest in cancer research and hold significant promise as diagnostic and prognostic biomarkers for malignant disease. MiR-362-5p have been found to exert both oncogenic and tumor suppressive effects depending highly on the cellular context. The aim of this study was to determine whether the expression of miR-362-5p can be served as a prognostic factor for patients with cytogentically normal acute myeloid leukemia (CN-AML). METHODS: We enrolled 224 patients with CN-AML and measured the expression of miR-362-5p by quantitative real time PCR analysis. We classified patients into high and low expression based on the median value. The Cox regression analyses were carried out to assess the prognostic significance of miR-362-5p expression in the context of the well-established predictors. Additionally, microRNA expression profiling were conducted to identify the biological insights between high and low group. RESULTS: High expressers had older age. High expressers obtained shorter overall survival in the univariate analysis. The independent prognostic value of miR-362-5p remained in the context of the well-established clinical and cytogenetic predictors. Moreover, the prognostic value of miR-362-5p was also validated in an independent cohort of CN-AML. Notably, numerous oncomiRs were also high expressed in high miR-362-5p group. CONCLUSION: High miR-362-5p expression was associated with poorer overall survival implicating the oncogenic function in AML development.
Assuntos
Análise Citogenética , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Feminino , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , PrognósticoRESUMO
Higher concentrations of rare earth (RE) ions in glass materials would be favorable for the output of single-frequency fiber lasers. In this Letter, we adjusted the topological structure of glass networks through controlling the numbers of non-bridging oxygens (NBOs) and bridging oxygens (BOs) by tuning the composition of the glasses, hence increasing the RE doping concentration of germanosilicate glasses. The increased flexibility of the glass networks favors the distribution of clusters of RE ions to decrease fluorescence quenching, which was validated by both our experimental and theoretical results. To the best of our knowledge, for the first time, a highly Er3+-doped (up to 7 mol. %) heavy metal oxide glass was fabricated without quenching by tuning the components of the glass. In addition, we have demonstrated an approach to enhance the fluorescence properties of heavily RE-doped glass materials by tailoring network topology.
RESUMO
The effects of Tm3+ concentration on upconversion emission and temperature-sensing behavior of Tm3+/Yb3+:Y2O3 nanocrystals were investigated. Blue and red emissions were observed under 980 nm excitation. Both upconversion emissions and the blue to red intensity ratio were found to decrease with increasing Tm3+ concentration. The temperature-sensing performances of the samples were studied, the fluorescence intensity ratio of 1G4(a)â3H6 (477 nm) and 1G4(b)â3H6 (490 nm) transitions from Tm3+ ions was chosen as the thermometric index. The results showed that the sensor sensitivity was sensitive to Tm3+ ion concentration. The maximum sensitivity of ~32 × 10-4 K-1 was obtained for 0.1%Tm3+/5%Yb3+:Y2O3 nanocrystals at 344 K. Moreover, a marked optical induced heating effect was also found in the nanocrystals. The prepared Tm3+/Yb3+:Y2O3 nanocrystals could be used in temperature-sensing probes and in optical heaters.
Assuntos
Nanopartículas/química , Óxidos/química , Temperatura , Túlio/análise , Itérbio/química , Ítrio/química , Luminescência , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
OBJECTIVE: To assess the value of fluorescence in situ hybridization (FISH) for the detection of genomic abnormalities among patients with chronic lymphocytic leukemia (CLL). METHODS: Interphase FISH was performed on bone marrow samples derived from 105 patients with CLL at the time of diagnosis using probes for D13S319/13q14, ATM/11q22, P53/17p13 and CEP12. The abnormalities and prognostic factors were analyzed. Overall survival of the patients was calculated. RESULTS: The FISH assay has detected genomic abnormalities in 81 (77.1%) of the patients, among which D13S319/13q14 deletion was the most common (49/105, 46.67%). 24(22.86%) patients had trisomy 12, 21(20.00%) had ATM/11q deletion, and 12(11.43%) had P53/17p deletion. A significant correlation was found between Binet staging and the detected abnormalities (< 0.05). With a median follow-up time of 10 months, 11 patients (10.5%) had died. Compared with those with P53 deletion, patients with 13q deletion showed a better overall survival. However, the overall survival did not significantly differ between patients with various genomic abnormalities (> 0.05). CONCLUSION: FISH is capable of detecting common genomic aberrations among patients with newly diagnosed CLL. Deletion of D13S319/13q14 is the most common aberration in such patients. Genomic aberrations are significantly correlated with Binet staging but not the overall survival of CLL patients.
Assuntos
Aberrações Cromossômicas , Hibridização in Situ Fluorescente/métodos , Leucemia Linfocítica Crônica de Células B/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVE: Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by ineffective hematopoiesis due to stem cell abnormalities. Monosomy 7q aberrations are a common cytogenetic abnormality in MDS. Specifically, an unbalanced translocation der(1;7)(q10;p10) [der(1;7)] has been identified in MDS patients, which is a monosomy 7q aberration variant like -7/del(7q). However, knowledge of der(1;7)'s features remains limited. Existing studies have compared the clinical and genetic characteristics of der(1;7) to those of -7/del(7q) but yielded inconsistent findings. Accordingly, we conducted meta-analyses comparing der(1;7) to -7/del(7q). METHODS: Publications were searched from the following databases up to January 10, 2023: Pubmed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov. Eligible studies were assessed for risks of bias. Relevant data were extracted from included studies and analyzed using random-effects models. Publication bias was evaluated and sensitivity analyses were performed. RESULTS: The comparative meta-analyses included 405 MDS patients with der(1;7) from nine studies. The analysis revealed that der(1;7) was associated with a greater male preponderance (86.1% vs. 68.3%, Odds Ratios (ORs) 2.007, p < 0.01) than -7/del(7q), lower platelets counts compared to del(7q), higher hemoglobin levels than -7, lower absolute neutrophil counts, and higher percentage of patients with non-excess blasts (66.9% vs. 41.3%, ORs 2.374, p = 0.01) in comparison with -7/del(7q). The der(1;7) existed more as a sole karyotype aberration (55.6% vs. 37.0%, ORs 2.902, p = 0.02), co-occurred more often with +8 (22.7% vs. 4.2%, ORs 5.714, p = 0.04) whereas less -5/del(5q) (1.5% vs. 41.3%, ORs 0.040, p < 0.01) and complex karyotype (7.3% vs. 54.8%, OR 0.085, p < 0.01). The der(1;7) was associated with higher frequencies of RUNX1 (40.8% vs. 12.3%, ORs 4.764, p < 0.01), ETNK1 (28.1% vs. 2.5%, ORs 42.106, p < 0.01) and EZH2 (24.8% vs. 6.9%, ORs 3.767, p = 0.02) mutations, but less TP53 mutation (2.4% vs. 45.3%, ORs 0.043, p < 0.01). Moreover, der(1;7) patients had longer time to progression (Hazard Ratios (HRs) 0.331, p = 0.02), better overall survival (OS) than -7 patients (HRs 0.557, p < 0.01), but similar OS with del(7q) patients (HRs 0.837, p = 0.37). CONCLUSION: The findings revealed distinct clinical, cytogenetic, and molecular characteristics distinguishing der(1;7) from -7/del(7q), indicating der(1;7) defines a unique subtype within MDS with monosomy 7q. These findings support classifying der(1;7) as a separate MDS entity in future.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 7 , Síndromes Mielodisplásicas , Síndromes Mielodisplásicas/genética , Humanos , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 1/genética , Masculino , Feminino , Translocação Genética , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The purpose of this preliminary investigation into the pathogenesis of pre-eclampsia was to screen the differential proteins in the serum of pregnant women with normal pregnancy and early-onset pre-eclampsia using isobaric tags for relative and absolute quantitation (iTRAQ), so as to identify serum biomarkers for the early diagnosis of pre-eclampsia. METHODS: We examined the peripheral serum of 58 normal pregnant women and 42 pregnant women with early-onset pre-eclampsia using iTRAQ; the differentially expressed proteins were screened for bioinformatics analysis; and the expression of candidate proteins human leukocyte antigen-1 (HLA-1) and ß2-microglobulin (ß2M) in placental tissues was detected using western blot. RESULTS: We identified a total of 63 differential proteins in the serum of patients from the normal control group and the pre-eclampsia group, and this included 24 up-regulated proteins and 39 down-regulated proteins. The western blot results of placental tissue showed reduced HLA-1 expression (1.12 ± 0.23) in the placenta in the pre-eclampsia group as compared with the normal control group (1.34 ± 0.22). Consistent with the results observed in the serum, ß2M in the placenta in the pre-eclampsia group was significantly elevated (1.05 ± 0.47) in comparison with the normal group (0.75 ± 0.33) (P < 0.05). CONCLUSION: In this study, we found that iTRAQ technology was useful for identifying differentially expressed proteins in the peripheral serum of pregnant women with pre-eclampsia, and that HLA-1 and ß2M, which may be involved in the occurrence of pre-eclampsia, show promise as predictive markers of pre-eclampsia.
Assuntos
Biomarcadores , Antígenos HLA , Placenta , Pré-Eclâmpsia , Microglobulina beta-2 , Adulto , Feminino , Humanos , Gravidez , Microglobulina beta-2/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Placenta/metabolismo , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Proteômica/métodos , Antígenos HLA/sangueRESUMO
OBJECTIVES: In patients with acute promyelocytic leukemia (APL), additional chromosomal abnormalities (ACAs) are prognostic indicators. However, the clinical features of ACAs were not systematically reported in Chinese patients. Therefore, we enrolled a large cohort of APLs to demonstrate the clinical characteristics and prognostic value of ACAs. METHODS: 268 patients with newly diagnosed APL with t(15;17)(q24;q21) were retrospectively enrolled, and their clinical characteristics and the predictive value of ACAs were assessed between patients with the presence and absence of ACAs. RESULTS: APL patients with and without ACAs did not differ significantly in their clinical features or treatment response and clinical outcomes like overall survival (OS) and disease-free survival (DFS). It appeared to be substantially associated with worse OS in APL patients with trisomy 8, which was the most common ACA, although DFS was unaffected. Interestingly, the presence of ACAs or trisomy 8 affected OS and DFS in the subgroup of patients aged ≥60 years; by contrast, ACAs had no effect on OS or DFS in any treatment subgroup (ATRA + ATO/RIF or ATRA + ATO/RIF + CH or ATRA + CH), except for the ATRA + ATO/RIF + CH treatment subgroup, where their impact on DFS was less favorable. CONCLUSIONS: Our results suggested that OS and DFS were unaffected by ACAs. Nonetheless, in the subgroup of patients older than 60, the existence of ACAs or trisomy 8 appeared to impact OS and DFS negatively. Individuals with t(15;17) alone had a higher DFS and were more susceptible to ATRA + ATO/RIF + CH than individuals with t(15;17) ACAs.
Assuntos
Arsenicais , Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína , Estudos Retrospectivos , Prognóstico , Aberrações Cromossômicas , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Immune checkpoint inhibitors (ICIs) are increasingly being used in the treatment of advanced human malignancies. ICIs-related adverse events, including pancreatitis and diabetes, have been individually characterized in the literature. The co-occurrence of ICIs-related pancreatitis with diabetes is rare and easily overlooked, but it is often severe or fatal. We present a patient with renal tumor resection who was treated with injection of the PD-L1 inhibitor toripalimab and eventually developed acute pancreatitis and fulminant type 1 diabetes mellitus. In addition, we conducted a literature review of ICIs-related pancreatitis with diabetes. The case in our report presented with paroxysmal abdominal pain and loss of appetite. Intravenous fluids and insulin infusion improved the patient's pancreatitis and explosive hyperglycemia. This article suggests that ICIs can affect endocrine and exocrine functions of the pancreas, while providing information and new perspectives for the diagnosis and treatment of this challenging rare disease, helping inspire clinicians for the early identification and effective management of similar cases.
Assuntos
Diabetes Mellitus Tipo 1 , Doenças do Sistema Endócrino , Neoplasias , Pancreatite , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Pancreatite/induzido quimicamente , Pancreatite/diagnóstico , Doença Aguda , Neoplasias/tratamento farmacológicoRESUMO
White-light diodes (WLEDs) are widely used in high-brightness applications owing to their outstanding advantages. However, current methods for preparing commercial WLEDs significantly deteriorate their optical properties and limit their use in high-power applications. To address this, inorganic materials, such as phosphor-in-glass (PiG), have been recently investigated as practical alternatives. In this study, a series of high-efficiency white-emitting PiG samples were prepared by mixing silicate glass powders with different particle size distributions and different concentrations of Y3Al5O12:Ce3+ (YAG:Ce3+) phosphors. The microstructure, transmittance, and photoluminescence properties of PiG were investigated. When the glass powder with the particle size ranges of 75-150 and 30-48 µm were mixed, at a ratio of 94 : 6, a silicate glass with a thickness of 0.8 mm and a maximum transmittance of 75% in the visible range was obtained. Under excitation with a 450 nm blue-light laser diode, PiG produced white light with a total luminescence efficiency of 194.64 lm W-1 and a total luminous flux of 623.9 lm. These results demonstrate that the optical performance of PiG can be effectively adjusted by adjusting the particle size distribution of silicate glass powder and the mixing concentration of the YAG:Ce3+ phosphor, thereby providing a tuning pathway for smart white-light devices.
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Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34+ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34+ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.
Assuntos
Acrilamidas , Plaquetas , Megacariócitos , Piperazinas , Pirimidinas , Acrilamidas/farmacologia , Animais , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Diferenciação Celular , Megacariócitos/citologia , Megacariócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Piperazinas/farmacologia , Pirimidinas/farmacologiaRESUMO
This study aimed to investigate the roles of the lysine (K)-specific demethylase 5C (KDM5C)-bone morphogenetic protein-7 (BMP-7) signaling pathway in the pathogenesis of severe preeclampsia (sPE). A total of 180 pregnant patients were enrolled in the study and classified into three groups: an early-onset sPE group (EOsPE) (n = 60), a late-onset sPE group (LOsPE) (n = 60), and a control group (normal pregnancy; n = 60). The messenger RNA (mRNA) and protein expression levels of bone morphogenetic protein receptor II (BMPRII), BMP-7, and KDM5C were detected in placenta samples from the two sPE groups, and their sites were evaluated using immunohistochemistry (IHC). The sPE groups showed an increased KDM5C mRNA expression, and the EOsPE group showed a decreased BMP-7 and BMPRII mRNA expression compared with the LOsPE group. However, contradictory results were discovered in terms of protein expression. Immunostaining of KDM5C, BMP-7, and BMPRII was observed in villous trophoblast and extravillous trophoblast cells. Compared with the control group, the staining intensity of KDM5C in the placental tissue trophoblast cell nucleus and vascular endothelial cells of the sPE groups was weaker, while that of BMP-7 and BMPRII was stronger, and the staining intensity was more subjective in the LOsPE group. Consistent findings were obtained by IHC and Western blot analysis. KDM5C nuclear-cytoplasmic translocation may regulate sPE through BMP-7 and its receptors. The KDM5C-BMP-7 signaling pathway may also lead to less invasion and increased apoptosis of the trophoblast cells, which is involved in the pathogenesis of sPE.
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Proteína Morfogenética Óssea 7 , Receptores de Proteínas Morfogenéticas Ósseas Tipo II , Histona Desmetilases , Pré-Eclâmpsia , Proteína Morfogenética Óssea 7/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Células Endoteliais/metabolismo , Feminino , Histona Desmetilases/genética , Humanos , Incidência , Lisina , Placenta/metabolismo , Pré-Eclâmpsia/genética , Gravidez , RNA Mensageiro/genéticaRESUMO
OBJECTIVE: To investigate the inhibitory effect of gonadotropin-releasing hormone II(GnRHII) and gonadotropin-releasing hormone I agonist (GnRH Ia) on the proliferation of endometrial stromal cells in vitro from endometriosis patients. METHODS: Different concentrations of GnRHII or GnRH Ia were added into the cultured endometrial stromal cells in vitro to detect the cell proliferation inhibition by MTT test. RESULTS: The inhibitory rate of GnRHII or GnRH Ia on eutopic and ectopic endometrial stromal cells in vitro was both dose- and time-dependent (P<0.05). Effect of GnRHII or GnRH Ia on the inhibitory rate of ectopic endometrial stromal cells was significantly higher than that of eutopic (P<0.05). GnRH II had a higher inhibitory rate on the endometrial stromal cells in vitro than did GnRH Ia (P<0.05). CONCLUSION: GnRHII has more antiproliferative effect on endometrial stromal cells than GnRH Ia in vitro, especially on ectopic endometrial stromal cells, suggesting that GnRHII may be more effective than GnRH Ia on endometriosis.
Assuntos
Endometriose/patologia , Endométrio/patologia , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/farmacologia , Células Estromais/patologia , Adulto , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Endométrio/metabolismo , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
Nowadays, there is enthusiastic effort to develop luminescent thermometers used for remote and high-sensitivity temperature readout over a wide sensing range. Herein, Pr3+ and Gd3+ co-doped ZrO2 nanocrystals are designed, prepared and investigated by XRD, Raman spectroscopy, XPS, TEM, EDS, DRS, PLE and PL spectroscopy. Upon 275 nm irradiation, the PL spectrum of ZrO2:Pr3+,Gd3+ is found to be composed of a narrow emission peak at 314 nm (Gd3+ 6P7/2-8S7/2), a broad defect-related emission band at 400 nm, and several emission peaks in the wavelength region of 585-700 nm (Pr3+ 1D2-3H4, 3P0-3H6, and 3P0-3F2), which exhibit different thermal responses owing to the effects of the various non-radiative relaxation processes and trap energy levels. Accordingly, the luminescence intensity ratio (LIR) between the Pr3+ 1D2-3H4 and Gd3+ 6P7/2-8S7/2 transitions demonstrates excellent relative sensing sensitivity values ((2.32 ± 0.01)% K-1-(8.32 ± 0.05)% K-1) and low temperature uncertainties (0.08 K-0.28 K) over a wide temperature sensing range of 303 K to 573 K, which are remarkably better than those of many other luminescence thermometers. What is discussed in the present study may be conducive to broadening the research region of RE3+ doped luminescence thermometric phosphors, especially for materials with rich 4f-4f transition lines and defect-related luminescence.
RESUMO
Mixed phenotype acute leukemia (MPAL) is an uncommon type of leukemia. It is one kind of malignant clonal diseases that expresses more than one genealogical specific antigen simultaneously. Most MPAL patients are associated with clonal chromosomal abnormalities and molecular genetic changes, such as t(9;22) (q34;q11) and KMT2A (MLL) rearrangement. These specific abnormalities usually have important guiding significance in MPAL diagnosis, targeted therapy and prognosis judgment. In this paper, we reported a case of MPAL, T/myeloid (M5) with an unfrequent combination of PML-RARα positivity and t(15;17). The treatment was successful with chemotherapy for both AML and ALL with daunorubicin, cytarabine (DA) and vincristine, prednisone (VP). We reported here this suggestive MPAL case of rare disease condition and effective treatment, in order to provide experience for the early diagnosis and treatment of similar patients.
RESUMO
The NUP214-ABL1 fusion gene is a constitutively active tyrosine kinase that can be detected in 6% of T-cell acute lymphoblastic leukemia (T-ALL) patients, and it can also be found in B-cell acute lymphoblastic leukaemia (B-ALL). However the NUP214-ABL1 fusion in acute myeloid leukemia (AML) has not yet been reported. Up to now, the sensitivity of NUP214-ABL1-positive patients to tyrosine kinase inhibitor (TKI) is still controversial. Here we report the first case of an AML patient carrying NUP214-ABL1 fusion gene. The conventional AML chemotherapy regimen for the patient was successful. Identification of additional AML patients with NUP214-ABL1 fusion gene will provide treatment experience and prognostic evaluation.