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Hepatic encephalopathy is a clinical syndrome of central nervous system dysfunction caused by liver insufficiency.It severely affects the quality of life of patients and may lead to death.Accurate prediction of the risk of developing hepatic encephalopathy is crucial for early intervention and treatment.In order to identify the risk of hepatic encephalopathy in patients in advance,many studies have been devoted to efforts to develop tools and methods to identify the risk of hepatic encephalopathy as early as possible,so as to develop preventive and early management strategies.Most conventional hepatic encephalopathy risk prediction models currently assess the prob-ability of a patient developing hepatic encephalopathy by analysing factors such as clinical data and biochemical indicators,however,their accuracy,sensitivity and positive predictive value are not high.The application of artificial intelligence to clinical predictive modelling is a very hot and promising area,which can use large amounts of data and complex algorithms to improve the accuracy and efficiency of diagnosis and prognosis.To date,there have been few studies using AI techniques to predict hepatic encephalopathy.Therefore,this paper reviews the research progress of hepatic encephalopathy risk prediction models,and also discusses the prospect of AI application in hepatic encephalopathy risk prediction models.It also points out the challenges and future research directions of AI in HE risk prediction model research in order to promote the development and clinical application of hepatic encephalopathy risk prediction models.
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Objective:To investigate the effect of sleep on physical performance and the correlation between sleep quality and physical performance in the elderly.Methods:In this prospective multicenter case-control study, 472 elderly people aged 60-80 years were recruited from three regions in China, Beijing, Tianjin, and Hainan Province.Basic information of study participants was collected through face-to-face interviews, and physical performance of study participants was assessed by the time up and go(TUG)test on site, with 106 cases(22.5%)in the normal physical performance group and 366 cases(77.5%)in the abnormal group.The Pittsburgh Sleep Quality Index(PSQI)and the Epworth Sleepiness Scale(ESS)were applied to assess sleep quality of study subjects.Correlation analysis was performed to examine factors affecting subjects' physical performance.Results:Age, history of alcohol consumption, BMI, past medical history, the ESS score, daytime sleepiness, and some components of PSQI, such as sleep quality, sleep efficiency, sleep disturbances, use of sleeping drugs and daytime dysfunction, were influencing factors of the TUG score.Two components of PSQI, sleep duration and habitual sleep efficiency, and the ESS score were positively correlated with physical performance.Logistic regression analysis showed that risk factors for decreased physical performance in the elderly included increased age( OR=1.125, 95% CI: 1.083-1.168, P<0.01), history of alcohol consumption( OR=0.482, 95% CI: 0.384-0.605, P<0.001), abnormally high body mass index( OR=1.663, 95% CI: 1.340-2.063, P<0.01), hyperlipemia( OR=0.156, 95% CI: 0.077-0.318, P<0.01), digestive system diseases( OR=0.154, 95% CI: 0.044-0.532, P<0.01), use of sleeping drugs( OR=0.415, 95% CI: 0.202-0.854, P<0.05), daytime sleepiness( OR=4.234, 95% CI: 2.800-6.403, P<0.01), a high habitual sleep efficiency score of PSQI( OR=1.425, 95% CI: 1.214-1.672, P<0.01)and a high sleep disturbances score in PSQI( OR=3.356, 95% CI: 2.337-4.819, P<0.01). Conclusions:The incidence of physical performance decline is high in the elderly.There is a correlation between physical performance and sleep quality.
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Objective@#To explore sex differences in 3D T1texture features in the progression of Alzheimer's disease (AD) and to predict the diagnosis of AD patients of different sex．@*Methods@#Seventy-seven AD patients (34 males and 42 females) ，74 amnestic mild cognitive impairment ( aMCI) patients ( 35 males and 39 females) and 75 healthy controls (HC) (35 males and 40 females) were recruited and high-resolution 3-dimensional T1 structural images were collected． Brain regions closely related to AD brain damage were selected as regions of interest ( ROIs) ，texture feature extraction and feature screening were performed．Analyses were performed by sex，and the support vector machine (SVM) was used for classification and prediction. @*Results @#In the AD vs HC，AD vs aMCI and aMCI VS HC groups by different sex，we obtained some brain regions with relatively high recognition index in different subgroups，and found that there were significant differences between female patients and male patients with high recognition index，and the recognition index of female patients ( area under the curve，accuracy，sensitivity and specificity were generally higher than that of male．@*Conclusion@#There are significant sex differences in texture features in AD process，and the classification and prediction ability of texture features in female patients is better， suggesting the importance of sex differences in AD research．This study provides some reliable biomarkers for early sex-specific identification of AD，which may be helpful for the early diagnosis and treatment of AD in the future.
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Objective To investigate the influencing factors for the prognosis of adult patients with chronic drug-induced liver injury (DILI). Methods A total of 255 patients who were diagnosed with chronic DILI by liver biopsy in The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to December 2018 were enrolled, and according to the liver function after 2 years, they were divided into non-recovery group and recovery group. The two groups were analyzed in terms of the clinical data including age, sex, body mass index, types of drugs used, type of DILI injury, severity of DILI injury, underlying diseases, laboratory markers, liver histology, and 2-year prognosis. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate logistic regression analyses were used to investigate the independent risk factors for the prognosis of chronic DILI. Results After 2 years of follow-up, 195 patients (76.5%) achieved the recovery of liver function, while 60 patients (23.5%) did not achieve such recovery. There were significant differences between the two groups in the type of DILI injury ( P =0.028), the proportion of patients with diabetes ( P =0.048), and the degree of liver fibrosis ( P 2×upper limit of normal (ULN) ( OR =3.080, 95% CI : 1.331-7.127, P =0.009) were independent risk factors for the prognosis of chronic DILI. Conclusion When patients meet the diagnostic criteria for chronic DILI, the independent risk factors PLT 2×ULN may be used to screen out the patients who are more likely to have poor prognosis.
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Although drug-induced liver injury (DILI) is often an acute process, about 20% of the patients may progress to chronic DILI. Chronic DILI has a long course of disease and there is still no effective treatment. With the development and clinical application of new drugs and the wide application of herbal and dietary supplements, the incidence rate of DILI chronicity gradually increases. This article overviews the latest research advances in DILI chronicity from the aspects of the epidemiology, risk factors, clinical manifestations, diagnosis, and treatment of DILI, so as to gain a comprehensive understanding of chronic DILI.
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Objective To learn the status of disabled elderly in community,and to analyze the influencing factors on activities of daily living. Methods With the method of cluster stratified random sampling, a self -designed questionnaire and Modified Barthel Index (MBI)was used in investigation of survival status and activities of daily living (ADL)of the elderly in community of Sijiqing Street,Jianggan District,Hangzhou City,and the logistic regression model was used to analyze its influencing factors.Results A total of 883 valid questionnaires were completed and analyzed,and 1 91 interviewees was found to be with disability according to the disability standards with the percentage 21 . 6%.Logistic regression analysis suggested that age(OR=4. 99,95%CI:4. 52-5. 66),chronic disease situation(OR=2. 1 9,95%CI:1. 74-2. 72),stroke(OR=3. 78,95%CI:2. 65 -5. 06),osteoarthritis(OR=1. 87,95%CI:1. 55 -2. 39),chronic bronchitis(OR=2. 1 7,95%CI:1 . 73-2. 91 ),visual(OR=1 . 73,95%CI:1 . 37 -2. 28),dementia(OR=1 . 92,95%CI:1 . 23-2. 69 ),lumbocrural pain (OR =2. 04,95%CI:1 . 47 -2. 89 )were the risk factors of disability.Educational background(OR=0. 87,95%CI:0. 82-0. 95),income(OR=0. 81 ,95%CI:0. 76 -0. 87),outdoor activity(OR=0. 69, 95%CI:0. 63-0. 81 ),physical exercise(OR=0. 67,95%CI:0. 56 -0. 79)were protective factors.Conclusion The status of disabled in community of Hangzhou affected by various factors,and it is necessary to provide them health management and comprehensive intervention.
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To determine whether the microRNAs (miRNAs) contained in cancer-derived microvesicles (MVs) mirror those of the parental tumor cells, we compared the miRNA expression profiles of MVs derived from their parental hepatocellular carcinoma (HCC) cells. The presence and levels of 888 miRNAs from SMMC-7721 cells and MVs were detected by Agilent miRNA microarray analysis. Four selected miRNAs were verified by real time qRT-PCR. Furthermore, the genes of the miRNAs were bioinformatically identified to explore potential roles of the miRNAs in HCC microenvironment. Our results showed that miRNAs expression profiles of MVs derived from HCC were significantly changed. Of all the miRNAs tested, 148 miRNAs were co-expressed in MVs and SMMC-7721 cells, only 121 and 15 miRNAs were detected in MVs and SMMC-7721 cells, respectively. Among the 148 co-expressing miRNAs, 48 miRNAs had the similar expression level and 6 of them were supposed to be oncogenic or suppressive miRNAs. According to the target prediction by Quantile Algorithm method, these miRNAs may regulate 3831 genes which were closely related to cell cycle, apoptosis and oncogenesis, and 78 were known tumor suppressors or oncogenes. Gene ontology (GO) analysis indicated that 3831 genes were mainly associated with nucleic acid binding, cell death, cell adhesion. MVs containing miRNAs, released into the HCC microenvironment, bear the characteristic miRNAs of the original cells and might participate in cancer progression.
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To determine whether the microRNAs (miRNAs) contained in cancer-derived microvesicles (MVs) mirror those of the parental tumor cells, we compared the miRNA expression profiles of MVs derived from their parental hepatocellular carcinoma (HCC) cells. The presence and levels of 888 miRNAs from SMMC-7721 cells and MVs were detected by Agilent miRNA microarray analysis. Four selected miRNAs were verified by real time qRT-PCR. Furthermore, the genes of the miRNAs were bioinformatically identified to explore potential roles of the miRNAs in HCC microenvironment. Our results showed that miRNAs expression profiles of MVs derived from HCC were significantly changed. Of all the miRNAs tested, 148 miRNAs were co-expressed in MVs and SMMC-7721 cells, only 121 and 15 miRNAs were detected in MVs and SMMC-7721 cells, respectively. Among the 148 co-expressing miRNAs, 48 miRNAs had the similar expression level and 6 of them were supposed to be oncogenic or suppressive miRNAs. According to the target prediction by Quantile Algorithm method, these miRNAs may regulate 3831 genes which were closely related to cell cycle, apoptosis and oncogenesis, and 78 were known tumor suppressors or oncogenes. Gene ontology (GO) analysis indicated that 3831 genes were mainly associated with nucleic acid binding, cell death, cell adhesion. MVs containing miRNAs, released into the HCC microenvironment, bear the characteristic miRNAs of the original cells and might participate in cancer progression.
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Humanos , Carcinoma Hepatocelular , Genética , Línea Celular Tumoral , Transformación Celular Neoplásica , Genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genética , Neoplasias Hepáticas , Genética , MicroARNs , Genética , Proteínas de Neoplasias , Genética , ARN Neoplásico , Genética , Vesículas Transportadoras , GenéticaRESUMEN
A female patient diagnosed with acute myelocytic leukemia M5a (AML-M5a) relapsed 986 days after her allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an unrelated male donor with matched human leukocyte antigen (HLA). Three re-induction chemotherapies were administered, and partial remission was achieved. The patient was given repetitive infusion of cytokine-induced killer (CIK) cells expanded from recipient peripheral mononuclear cells of full donor chimerism due to loss of contact of quondam donor for donor lymphocyte infusion (DLI) and rejection of second transplantation. The patient achieved complete cytogenetical remission. This strategy might overcome the obstacle of donor unavailability and present an appealing new therapeutic alternative to donor-recruited adoptive immunotherapy for relapsed disease at post-transplantation.
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Adulto , Femenino , Humanos , Células Asesinas Inducidas por Citocinas , Trasplante , Trasplante de Células Madre Hematopoyéticas , Leucemia , TerapéuticaRESUMEN
To study the expressions of CD34 and CD117 in the tissues of hepatocelluar carcinoma (HCC) and to explore the relationship with clinical pathology and it's evaluation on the prognosis of HCC patients. The expressions of CD34 and CD117 were examined by two-step methods of PV-9000 of immunohistochemistry in 55 HCC cases, 10 liver cirrhotic specimens and 6 normal liver specimens. Clinical-pathological data, tumor recurrent rate and survival rate after hepatectomy were recorded and analyzed with Fisher's Exact Test, Pearson X2 Test, Kaplan-Meier, Log-Rank Test and Cox Regression. The positive expression of CD34 was found in 65.4% of HCC, 20% of cirrhostic liver specimens and 16.7% of normal liver specimens, respectively. Significant differences found among the three groups, and the CD34 expression was significantly associated with vessel embolus (X2 = 4.000, P = 0.046) and the histological grades (X2 = 11.008, P = 0.001). The positive expression of CD117 was 47.3%, 10% and 0% in HCC, cirrhotic liver specimens and normal liver tissues, respectively, and statistical differences esxisted among the three groups. The CD117 expression was dramatically related to the histological grades (X2 = 5.115, P = 0.024) and clinical stages (X2 = 15.459, P = 0.000). Median disease free survival time after hepatectomy was significantly shorter in the group with positive-expression of CD34 (X2 = 4.105, P = 0.043) and CD117 (X2 = 28.023, P = 0.000) than the negative-expressed groups, respectively. Multivariate analysis showed that CD117 expression status, serum AFP levels and the size of tumor were independently prognostic factors for HCC patients. Tthe results demonstrated that CD34 and CD117 might play an important role in liver carcinogenesis and the progression of HCC, and they might potentially serve as markers for HCC prognosis.
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Humanos , Carcinoma Hepatocelular , Hepatectomía , Estimación de Kaplan-Meier , Neoplasias Hepáticas , Recurrencia Local de NeoplasiaRESUMEN
<p><b>OBJECTIVE</b>To analysis the clinic and genotype in two Chinese patients with Dyskeratosis congenita (DC).</p><p><b>METHODS</b>The two patients were characterized by mucocutaneous abnormalities (abnormal nails, lacey reticular pigmentation, and oral leukoplakia), bone marrow failure. They were diagnosed with DC. DC genes were amplified by polymerase chain reaction (PCR), including DKC1, TERT, TERC, TINF2, NOP10, NHP2, then DNA sequencing was performed for abnormal exons.</p><p><b>RESULTS</b>An abnormal peak was found in exon 6 of TINF2 gene of the two patients. DNA sequencing showed a 845G→A transition in TINF2 gene in the two patients.</p><p><b>CONCLUSION</b>We should think about DC if the young patients with mucocutaneous abnormalities and marrow failure. TINF2 c.845G→A(R282H) does exist in the two patients. It is reported in China for the first time.</p>
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Preescolar , Femenino , Humanos , Lactante , Masculino , Secuencia de Bases , Análisis Mutacional de ADN , Disqueratosis Congénita , Diagnóstico , Genética , Exones , Proteínas de Unión a Telómeros , GenéticaRESUMEN
In order to investigate the molecular mechanisms of SARI expression regulation in chronic myeloid leukemia (CML), 46 patients with CML and 40 healthy volunteers were recruited in this study. SARI expression in the peripheral blood mononuclear cells (PBMNC) of CML patients and healthy volunteers was assayed by using real-time quantitative PCR. K562 cells were in vitro incubated with the BCR-ABL inhibitor STI571 (imatinib) at 37°C and 5% CO2 for 24 hours, then SARI expression was detected by using real-time quantitative PCR. All experiments were repeated three times. The results showed that as compared with healthy volunteers, the expression of SARI mRNA in PBMNC of CML patients presented a lower level (p < 0.001). After exposure of K562 cells to STI571 (2.5 µmol/L) for 24 hours, the SARI expression was higher than that in K562 cells treated without STI571 (p < 0.001). It is concluded that the suppression of SARI expression is involved in CML pathogenesis, and BCR-ABL mediates the down-regulation of SARI mRNA expression in K562 cells. These findings suggest a new orientation for gene therapy in CML patients.
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Humanos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Genética , Benzamidas , Proteínas de Fusión bcr-abl , Regulación Leucémica de la Expresión Génica , Mesilato de Imatinib , Células K562 , Piperazinas , Farmacología , Pirimidinas , Farmacología , Proteínas Supresoras de Tumor , GenéticaRESUMEN
The aim of this study was to investigate the apoptosis-inducing effect of cinnamic aldehyde (CA) on chronic myeloid leukemic (CML) cells and its mechanism. K562 cells and primary bone marrow mononuclear cells (MNC) from patients with CML were treated by various concentrations of CA. Flow cytometry was employed to measure the apoptosis of K562 cells and primary CML bone marrow MNC. Western blot was used to determine the expression of C-MYC and the phosphorylation of CrkL in K562 cells, and real-time polymerase chain reaction (real-time PCR) was used to quantify the expression of BCR-ABL mRNA in K562 cells. The results indicated that CA induced the apoptosis of K562 cells in a time- and dose-dependent manner. CA induced apoptosis of CML MNC dose-dependently. CA inhibited the expression of BCR-ABL mRNA and C-MYC, reduced CrkL phosphorylation levels in K562 cells. It is concluded that CA induces apoptosis of CML cells in vitro. Down-regulation of the expression and function of BCR-ABL may be one of its most important anti-leukemia mechanisms.
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Humanos , Acroleína , Farmacología , Apoptosis , Proteínas de Fusión bcr-abl , Metabolismo , Regulación Leucémica de la Expresión Génica , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva , Metabolismo , PatologíaRESUMEN
In order to investigate the effect of PP2A activator and PP2A inhibitor on proliferation of HL-60 cells and analyze the changes of PP2A activity in patients with acute myeloid leukemia (AML), HL-60 cells were treated with FTY720 alone or in combination with okadaic acid (OA) for 24 hours in culture. Cell proliferation was assayed with CCK8 kit. In addition, 20 AML patients including de novo AML and relapsed AML were enrolled in this study. The activity of PP2A in the peripheral blood mononuclear cells of patients was assayed with a PP2A Immunoprecipitation Phosphatase Assay Kit, the data were analyzed by software SPSS 16.0. The results indicated that as compared with control group, the proliferation of cells in FTY720 group was obviously inhibited (p < 0.05). The proliferation of cells in FTY720 + OA group was slightly inhibited as compared with the control group, there was no statistical difference (p > 0.05), but there was significant difference between the FTY720 + OA and FTY720 groups (p < 0.05). The activity of PP2A in AML patients (453.67 ± 102.52 pmol phosphate) was obviously lower than that in the normal controls (673.29 ± 96.32 pmol phosphate), there was significant difference between them (p < 0.01). It is concluded that the activation or inhibition of PP2A can affect the proliferation of HL-60 cells in vitro. Compared with healthy individuals, the activity of PP2A in AML patients is obviously lower. PP2A protein playing a key role in the occurrence and development of AML may be valuable for the diagnosis and treatment of AML.
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Apoptosis , Estudios de Casos y Controles , Proliferación Celular , Activadores de Enzimas , Farmacología , Inhibidores Enzimáticos , Farmacología , Clorhidrato de Fingolimod , Células HL-60 , Leucemia Mieloide Aguda , Metabolismo , Ácido Ocadaico , Farmacología , Glicoles de Propileno , Farmacología , Proteína Fosfatasa 2 , Metabolismo , Esfingosina , FarmacologíaRESUMEN
The expression of immunological markers of one hematopoietic lineage on the abnormal cells of another lineage (cross-lineage expression) is a known feature of leukemia. The present study was aimed to investigate the cross-lineage expression in ALL cells. The cross-lineage expression in ALL cells from 505 patients was detected by flow cytometry using 23 monoclonal antibodies (McAbs) in triple staining combinations. The results showed that in whole ALL, the expression of myeloid antigens occurred in 56.4% of the cases, and CD13 was the most frequently expressed myeloid marker (32.7%) followed by CD33 (29.5%), CD15 (19.2%) and CD11b (7.7%). CD13/CD33 expressions were more frequent in CD34(+) cases than in CD34(-) cases. In B-ALL, T-cell antigen CD4, CD5, CD7 and CD2 were found in 27 (6.3%), 12 (2.8%), 8 (1.9%), and 6 (1.4%) cases respectively, and CD7(+), CD2(+) and CD4(+) cases commonly expressed CD13/CD33. In T-ALL, B-cell antigen cCD79a, CD19 and CD22 were found in 6 (8.1%), 5 (6.8%), and 2 (2.8%) cases respectively, and all of CD19(+) and CD22(+) cases were all accompanied with CD13/CD33. It is concluded that cross-lineage expression in ALL mostly exists in the immature stages, ALL cells more frequently express phenotypes B(+)M(+), T(+)M(+) and occasionally B(+)T(+)M(+), but B(+)T(+)M(-) phenotype is extremely rare.
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Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto Joven , Antígenos CD , Metabolismo , Citometría de Flujo , Métodos , Inmunofenotipificación , Leucemia-Linfoma Linfoblástico de Células Precursoras , Alergia e Inmunología , MetabolismoRESUMEN
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. The expressions of JunB and CDH13 (cadherin-13) gene as tumor suppressor gene were inactivated by promoter methylation in CML patients. This study was purposed to investigate the methylation difference of JunB and CDH13 gene promoter and the expression levels of JunB and CDH13 gene in CD34(+)CD38(-) cells in CML patients vs normal individuals. CD34(+)CD38(-) cells from 8 cases of CML and 5 normal individuals were selected by flow cytometry. The methylation status of JunB and CDH13 genes were detected by MS-PCR in selected CD34(+)CD38(-) cells. The expression levels of JunB and CDH13 gene was detected with real time polymerase chain reaction (RT-PCR). The results showed that no methylation of JunB and CDH13 gene was detected in CD34(+)CD38(-) cells of 5 normal individuals. Methylations of JunB and CDH13 promoter were found in 87.5% (7/8) and 50% (4/8) CML CD34(+)CD38(-) cells, percentages of which were significantly higher than those in normal individuals. The difference was statistically significant (p < 0.05). The relative expression levels of JunB and CDH13 mRNA in CD34(+)CD38(-) cells of CML patients were significantly lower than those in normal individuals (2(-DeltaDeltaCT) were 1/5.21 and 1/10.63 respectively). It is concluded that the high methylation of JunB and CDH13 gene promoter occurs in CD34(+)CD38(-) cells of CML patients, their mRNA expression level is significantly lower, thus the methylation of JunB and CDH13 gene promoter probably plays a role in the pathogenesis of CML and may have clinical significance in predicting prognosis of CML.
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , ADP-Ribosil Ciclasa 1 , Alergia e Inmunología , Antígenos CD34 , Alergia e Inmunología , Cadherinas , Genética , Metilación de ADN , Leucemia Mielógena Crónica BCR-ABL Positiva , Genética , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-jun , GenéticaRESUMEN
To establish a basis for deep investigation of the role of microRNA (miRNA) in the regulation of hematopoiesis, differential expression profiles of miRNA between human cord blood CD34(+)CD38(-) and CD34(+)CD38(+) cells were analyzed. Mononuclear cells from cord blood (CB) of healthy donors were separated by Ficoll-Hypaque density gradients. CD34(+)CD38(-) and CD34(+)CD38(+) cells were sorted by using FACS Vantage SE. Their mRNA were then extracted and hybridized to miRNA microarray chip. The resulting data were analyzed with GeneSpring and informatics technique. The results showed that eleven miRNAs were found to be downregulated and 73 miRNAs to be upregulated by at least two-fold in the CD34(+)CD38(+) cells of CB, compared with the CD34(+)CD38(-) cells, which maintained CD34(+)CD38(-) cells' self-renewal and multiple lineage potential, that were defined as "stemness" miRNAs. 12 of the 84 genes (14.29%) were common to 33 hematopoietic-expressed miRNAs expressed by CD34(+) cells from both peripheral blood and bone marrow in Georgantas's study, which included 10 upregulated miRNAs (hsa-miR-23b, -26b, -92, -107, -130a, -181a, -197, -213, -222, -223) and 2 downregulated ones (hsa-miR-16a, -155). Some "stemness" miRNAs undergo CD34 antigen-like expression pattern during development and commmitted differeniation of hematopoietic stem cell/progenitors. Hematopoiesis-associated miRNA clusters and putative target genes could be found with informatics technique. It is concluded that the hematopoietic "stemness" miRNAs play important roles in normal hematopoiesis: miRNA expression profiles of hematopoietic stem cell/progenitors --> their gene expression profiles --> their self-renewal and lineage-commmitted differeniation.
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Humanos , ADP-Ribosil Ciclasa 1 , Alergia e Inmunología , Antígenos CD34 , Alergia e Inmunología , Sangre Fetal , Alergia e Inmunología , Metabolismo , Perfilación de la Expresión Génica , Células Madre Hematopoyéticas , Biología Celular , Alergia e Inmunología , Fisiología , MicroARNs , Genética , MetabolismoRESUMEN
In order to investigate the expression and functional role of HERG1 K+ channels in leukemic cells and leukemic stem cells (LSCs), RT-PCR was used to detect the HERG1 K+ channels expression in leukemic cells and LSCs. The functional role of HERG1 K+ channels in leukemic cell proliferation was measured by MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. The results showed that herg mRNA was expressed in CD34+/CD38-, CD123+ LSCs but not in circulating CD34+ cells. Herg mRNA was also up-regulated in leukemia cell lines K562 and HL60 as well as almost all the primary leukemic cells while not in normal peripheral blood mononuclear cells (PBMNCs) and the expression of herg mRNA was not associated with the clinical and cytogenetic features of leukemia. In addition, leukemic cell proliferation was dramatically inhibited by HERG K+ channel special inhibitor E-4031. Moreover, E-4031 suppressed the cell growth by inducing a specific block at the G1/S transition phase of the cell cycle but had no effect on apoptosis in leukemic cells. The results suggested that HERG1 K+ channels could regulate leukemic cells proliferation and were necessary for leukemic cells to proceed with the cell cycle. HERG1 K+ channels may also have oncogenic potential and may be a biomarker for diagnosis of leukemia and a novel potential pharmacological target for leukemia therapy.
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In order to investigate the expression and functional role of HERG1 K+ channels in leukemic cells and leukemic stem cells (LSCs), RT-PCR was used to detect the HERG1 K+ channels expression in leukemic cells and LSCs. The functional role of HERG1 K+ channels in leukemic cell proliferation was measured by MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. The results showed that herg mRNA was expressed in CD34+/CD38-, CD123+ LSCs but not in circulating CD34+ cells. Herg mRNA was also up-regulated in leukemia cell lines K562 and HL60 as well as almost all the primary leukemic cells while not in normal peripheral blood mononuclear cells (PBMNCs) and the expression of herg mRNA was not associated with the clinical and cytogenetic features of leukemia. In addition, leukemic cell proliferation was dramatically inhibited by HERG K+ channel special inhibitor E-4031. Moreover, E-4031 suppressed the cell growth by inducing a specific block at the G1/S transition phase of the cell cycle but had no effect on apoptosis in leukemic cells. The results suggested that HERG1 K+ channels could regulate leukemic cells proliferation and were necessary for leukemic cells to proceed with the cell cycle. HERG1 K+ channels may also have oncogenic potential and may be a biomarker for diagnosis of leukemia and a novel potential pharmacological target for leukemia therapy.
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CCL23 is a human CC chemokine with potential suppression effects on both human and murine myeloid progenitor cells both in vitro and in vivo, and only expressed and released by dendritic cells differentiated from monocytes in blood cells. However, recent study has shown that CCL23 was over-expressed in bone marrow and peripheral blood cells from pediatric patients with acute myeloid leukemia (AML). In order to investigate the effects of CCL23 on the development, therapy and prognosis of leukemia, the U937 cells, a leukemic cell strain, were adopted and cultured with rhCCL23 for 72 hours. The cell proliferation and apoptosis rate were detected by Cell Counting Kit-8 and FITC-AnnexinV/PI respectively; the morphologic changes and the expression of CCR1 (the only receptor of CCL23 known by now) were observed during the differentiation process. The results showed that no obvious effect on the proliferation, apoptosis and differentiation of U937 was found by using CCL23 alone (P > 0.05), but cultured in combination with CCL23 and PMA, the differentiation of U937 cells were promoted remarkably, during which the CCR1 expression increased (P < 0.05). It is concluded that CCL23 alone did not inhibit the proliferation and differentiation of U937, while its use in combination with PMA may possess synergistic effect on inducting differentiation of U937 through the increase of receptor CCR1 expression.