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1.
Eur J Pediatr ; 183(2): 875-882, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37938353

RESUMO

Magnetic resonance imaging (MRI) T2* is the gold standard for detecting iron deposition in cardiac tissue, but the technique has limitations and cannot be fully performed in paediatric thalassemia patients. The aim of this study was to analyse clinical data to identify other predictors of cardiac iron deposition. A retrospective analysis was performed on 370 children with ß-TM. According to the cardiac MRI results, patients were allocated to a cardiac deposition group and noncardiac deposition group. Multivariate analysis revealed that genotype and corrected QT interval were associated with cardiac iron deposition, indicating that the-ß0/ß0 genotype conferred greater susceptibility to cardiac iron deposition. Receiver operating characteristic curve (ROC) analysis was performed, and the area under the curve (AUC) of genotype was 0.651. The AUC for the corrected QT interval was 0.711, at a cut-off value of 418.5 ms. ROC analysis of the combined genotype and corrected QT interval showed an AUC of 0.762 with 81.3% sensitivity and 64.7% specificity. Compared to patients with the ß+/ß+ and ß0ß+ genotypes, ß0ß0 children with ß-TM were more likely to have cardiac iron deposition.  Conclusion: The genotype and QTc interval can be used to predict cardiac iron deposition in children with ß-TM who are unable to undergo MRI T2 testing.


Assuntos
Sobrecarga de Ferro , Talassemia beta , Humanos , Criança , Talassemia beta/complicações , Talassemia beta/diagnóstico , Talassemia beta/genética , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/patologia , Estudos Retrospectivos , Curva ROC , Imageamento por Ressonância Magnética/métodos , Ferro , Miocárdio/patologia
2.
J Sci Food Agric ; 104(2): 1116-1131, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37740718

RESUMO

BACKGROUND: ß-Glucans are widely sourced and have various physiological effects, including anti-inflammatory effects. However, the strength of the anti-inflammatory activity of ß-glucans from different sources remains unknown due to the lack of rapid and effective biomarkers. This study therefore aimed to screen out the ß-glucans with strong anti-inflammatory activity from five different sources and to further screen out possible biomarkers in metabolites after fermenting the ß-glucans with gut microorganisms. RESULTS: The results showed that all five ß-glucans inhibited the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators and suppressed the mRNA expression level of TLR4/MyD88. Their anti-inflammatory mechanisms involved the inhibition of intracellular reactive oxygen species (ROS) production and suppression of mRNA expression of the NF-κB pathway and JNK pathway. Among them, barley ß-glucan exhibited the strongest anti-inflammatory effect, followed by Ganoderma lucidum ß-glucan. Enhanced anti-inflammatory activity of ß-glucan was found after fermentation and may be related to the increased abundance of metabolites such as vanillin, dihydroxyphenylacetic acid, caffeic acid, acetic acid, butyric acid, and lactic acid. They were strongly positively correlated to the abundance of beneficial bacteria such as Blautia, suggesting that the production of those metabolites may be responsible for the flourishing of the beneficial bacteria. CONCLUSION: In conclusion, barley was a preferred raw material for the preparation of ß-glucans with strong anti-inflammatory activity. Vanillin, dihydroxyphenylacetic acid, caffeic acid, acetic acid, butyric acid, and lactic acid were the possible biomarkers that could be utilized to evaluate the anti-inflammatory effect of ß-glucans. © 2023 Society of Chemical Industry.


Assuntos
beta-Glucanas , beta-Glucanas/metabolismo , Fermentação , Ácido Butírico , Anti-Inflamatórios/farmacologia , Bactérias/genética , Bactérias/metabolismo , Biomarcadores/metabolismo , Ácido Láctico , RNA Mensageiro/metabolismo
3.
Crit Rev Food Sci Nutr ; 62(30): 8319-8334, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34036843

RESUMO

There is a growing scientific view that the improvement of cancer by nonstarch polysaccharides (NSPs) is mediated by intestinal microbiota. Intestinal bacteria affect the supply of methyl donor substances and influence N6-methyladenosine (m6A) RNA methylation. As one of the epigenetic/epitranscriptomic modifications, m6A RNA methylation is closely related to the initiation and progression of cancers. This review summarizes the cancer-improving effects of NSPs through modulation of intestinal microbiota. It also summarizes the relationship between intestinal bacteria and the supply of methyl donor substances. Moreover, it also provides a summary of the effects of m6A RNA methylation on various types of cancer. The proposed mechanism is that, dietary consumed NSPs are utilized by specific intestinal bacteria and further reshape the microbial structure. Methyl donor substances will be directly or indirectly generated by the reshaped-microbiota, and affect the m6A RNA methylation of cancer-related and pro-carcinogenic inflammatory cytokine genes. Therefore, NSPs may change the m6A RNA methylation by affecting the methyl donor supply produced by intestinal microbiota and ameliorate cancer. This review discussed the possibility of cancer improvement of bioactive NSPs achieved by impacting RNA methylation via the intestinal microbiota, and it will offer new insights for the application of NSPs toward specific cancer prevention.


Assuntos
Microbioma Gastrointestinal , Neoplasias , Humanos , Metilação , Polissacarídeos , Neoplasias/prevenção & controle , Neoplasias/genética , RNA/genética
4.
J Sci Food Agric ; 102(14): 6432-6442, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35567370

RESUMO

BACKGROUND: Aging causes decreased antioxidant capacity and chronic inflammation and may even elevate cancer risks. Previous studies reported that flaxseed oil (FO) can alleviate age-related diseases, including improving alcoholic liver disease, atherosclerosis and diabetes. However, whether the intestinal microbiota accountable for this alleviation is still unknown. This study aims to study the antioxidant effects of FO in an aging rat model and the underlying mechanism between the intestinal microbiota and aging. RESULTS: Our results presented that serum and liver antioxidant capacities in FO group were up-regulated, and liver inflammation in FO group was reduced. The 16S rDNA sequencing showed that FO regulated the microbial community, including up-regulation of four families of Lactobacillus and six families of Clostridium. In addition, FO had also adjusted the relative abundance of several genera such as Ruminococcaceae_UCG-005 and Prevotella_9, which may be the key bacteria associated with the aging process. Colonic transcriptome analysis showed that there were 1679 differentially expressed genes (DEGs) in the Model group and the FO group (134 up-regulated and 1545 down-regulated). Gene set enrichment analysis (GSEA) revealed FO down-regulates the expression of the upstream genes Ptprc, Lck, Zap70, Lat and Lcp2 in the T cell receptor signaling pathway. CONCLUSION: In conclusion, FO improved antioxidant capacity and reduced intestinal microbial disturbances caused by aging damage, indicating that dietary FO has the potential to fight aging damage. This study provides a more comprehensive view of dietary intervention to improve aging. © 2022 Society of Chemical Industry.


Assuntos
Microbioma Gastrointestinal , Óleo de Semente do Linho , Envelhecimento , Animais , Antioxidantes/farmacologia , DNA Ribossômico/farmacologia , Galactose/efeitos adversos , Inflamação , Estresse Oxidativo , Ratos , Receptores de Antígenos de Linfócitos T
5.
Med Sci Monit ; 27: e929431, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33764958

RESUMO

BACKGROUND Enzymatically inactive chitinase-like protein CHI3L1 is overexpressed in diffuse large B cell lymphoma (DLBCL) patients with PD-L1 imbalance and promotes tumor progression in the microenvironment. Based on this, we investigated how CHI3L1 acts on the proliferation and apoptosis of DLBCL and whether there is a synergy of CHI3L1 in combination with anti-PD-L1 antibodies in vivo. MATERIAL AND METHODS CHI3L1 was detected by quantitative real-time PCR (RT-PCR) and western blot (WB) in B-lymphoma cell lines. CHI3L1 interference plasmids were constructed, and the levels of proliferation, cell cycle, apoptosis, and cell survival were examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model by RT-PCR, WB, CCK-8, and flow cytometry. RESULTS CHI3L1 was significantly expressed in SU-DHL-4 cells. CHI3L1-interfered RNA ShRNA-CHI3L1-1 was chosen to be used in the next experiment because it had a better interference effect. Dampened cell proliferation level, arrested cell cycle, reduced protein expressions of cyclin D1 and cyclin D2, and promoted cell apoptosis level were observed after SU-DHL-4 was transfected with ShRNA-CHI3L1-1. Furthermore, we also noticed increased expression of Bcl-2, decreased expressions of bax, cleaved caspase 3 and cleaved PARP, promoted cell survival-related protein p53, and reduced survivin. CONCLUSIONS This study demonstrated that knockdown of CHI3L1 inhibits cancer cell proliferation by regulating cell cycles, promotes cancer cell apoptosis, and enhances the pro-apoptotic effect of anti-PD-L1 antibody both in vivo and in vitro in DLBCL.


Assuntos
Anticorpos Bloqueadores/farmacologia , Linfócitos B/patologia , Antígeno B7-H1/metabolismo , Proteína 1 Semelhante à Quitinase-3/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteína 1 Semelhante à Quitinase-3/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Tolerância Imunológica , Linfoma Difuso de Grandes Células B/genética , Mutação/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/genética , Microambiente Tumoral , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
6.
Biol Blood Marrow Transplant ; 25(10): 2040-2044, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31207293

RESUMO

As an inherited anemia, thalassemia major (TM) is currently only curable with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here we report an allo-HSCT protocol for patients with TM who received a combination of granulocyte colony-stimulating factor-primed bone marrow and peripheral blood stem cells (G-BM & PBSCs) from a matched sibling donor (MSD). The conditioning regimen consisted of i.v. busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin. Chimerism analysis was performed for all patients. Immunosuppressive treatment was terminated if rejection was suspected, and donor lymphocyte infusion was administered once no response was observed. A total of 184 patients with TM were enrolled in the study between July 2007 and July 2018. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 13.1%, and that of moderate or severe chronic GVHD was 5.7%. The cumulative incidence of graft rejection was .6%. In the total cohort, the 3-year overall survival, thalassemia-free survival, and GVHD-free, relapse-free survival were 97.8%, 97.3%, and 89.5%, respectively. Collectively, our results indicate that G-BM & PBSCs from an MSD is be a good stem cell source for patients with TM undergoing allo-HSCT.


Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Talassemia beta/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Masculino , Estudos Prospectivos , Irmãos , Adulto Jovem
8.
Cell Physiol Biochem ; 47(5): 1989-1997, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29969779

RESUMO

BACKGROUND/AIMS: Thiamine-responsive megaloblastic anemia syndrome is a rare autosomal recessive disorder resulting from mutations in SLC19A2, and is mainly characterized by megaloblastic anemia, diabetes, and progressive sensorineural hearing loss. METHODS: We study a Chinese Zhuang ethnicity family with thiamine-responsive megaloblastic anemia. The proband of the study presented with anemia and diabetes, similar to his late brother, as well as visual impairment. All clinical manifestations were corrected with thiamine (30 mg/d) supplementation for 1-3 months, except for visual impairment, which was irreversible. The presence of mutations in all exons and the flanking sequences of the SLC19A2 gene were analyzed in this family based on the proband's and his brother's clinical data. Computer analysis and prediction of the protein conformation of mutant THTR-1. The relative concentration of thiamine pyrophosphate in the proband's whole blood before and after initiation of thiamine supplement was measured by high performance liquid chromatography (HPLC). RESULTS: Gene sequencing showed a homozygous mutation in exon 6 of the SLC19A2 gene (c.1409insT) in the proband. His parents and sister were diagnosed as heterozygous carriers of the c.1409insT mutation. Computer simulation showed that the mutations caused a change in protein conformation. HPLC results suggested that the relative concentration of thiamine pyrophosphate in the proband's whole blood after thiamine supplement was significantly different (P=0.016) from that at baseline. CONCLUSIONS: This novel homozygous mutation (c.1409insT) caused the onset of thiamine-responsive megaloblastic anemia in the proband.


Assuntos
Anemia Megaloblástica/genética , Diabetes Mellitus/genética , Éxons , Perda Auditiva Neurossensorial/genética , Proteínas de Membrana Transportadoras/genética , Mutação , Deficiência de Tiamina/congênito , Anemia Megaloblástica/etnologia , Anemia Megaloblástica/metabolismo , Anemia Megaloblástica/patologia , Povo Asiático , China/etnologia , Diabetes Mellitus/etnologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Feminino , Perda Auditiva Neurossensorial/etnologia , Perda Auditiva Neurossensorial/metabolismo , Perda Auditiva Neurossensorial/patologia , Humanos , Lactente , Masculino , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/metabolismo , Deficiência de Tiamina/etnologia , Deficiência de Tiamina/genética , Deficiência de Tiamina/metabolismo , Deficiência de Tiamina/patologia
9.
Mol Genet Genomics ; 293(1): 207-216, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28983712

RESUMO

Foetal haemoglobin (HbF) plays a dominant role in ameliorating the morbidity and mortality of ß-thalassaemia. A better understanding of the loci and genes involved in HbF expression would be beneficial for the treatment of ß-thalassaemia major. However, the genes associated with HbF expression remain largely unknown. In this study, we first explored large-scale data sets and examined the human genome for evidence of positive natural selection to screen out single nucleotide polymorphisms (SNPs). A genetic analysis of HbF levels was conducted in a Chinese cohort of patients with ß-thalassaemia to confirm the bioinformatics results. A total of 1141 subjects with ß-thalassaemia were recruited. The results showed that the SNP rs11759328 in the ARHGAP18 gene was significantly associated with HbF levels (Ρ = 5.1 × 10-4). ARHGAP18 belongs to the RhoGAP family and controls angiogenesis, cellular morphology and motility. Second, after determining that ARHGAP18 was highly expressed in the human K562 cell line, we used lentiviral-mediated small interfering RNA to knock down ARHGAP18 expression and subsequently assessed cell proliferation and apoptosis using cell proliferation assays and flow cytometry, respectively. ARHGAP18 downregulation in K562 cells significantly increased HBG1/2 expression and apoptosis, but proliferation was not significantly affected in vitro. Our data suggest that ARHGAP18, which was located by the SNP rs11759328 via positive selection, plays a potential role in regulating HbF expression in ß-thalassaemia and may be a promising therapeutic target. Knockout studies of ARHGAP18 warrant further investigation into its aetiology in HbF.


Assuntos
Hemoglobina Fetal/genética , Proteínas Ativadoras de GTPase/genética , Seleção Genética/genética , Talassemia beta/genética , Adolescente , Adulto , Apoptose/genética , Proliferação de Células/genética , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica/genética , Técnicas de Inativação de Genes , Estudos de Associação Genética , Humanos , Células K562 , Lentivirus/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem , Talassemia beta/sangue , Talassemia beta/patologia
10.
Pediatr Transplant ; 22(2)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29349879

RESUMO

This study's purposes were to diagnose intractable hemolytic anemia and to provide guiding treatment for the affected family members. We performed NGS in a panel of 600 genes for blood diseases on a patient with obscure hemolytic anemia and her parents. We confirmed the diagnosis of pyruvate kinase deficiency, identified a novel homozygous mutation of the PKLR gene (NM_000298: exon 6: c.T941C: p.I314T), and ruled out other blood diseases in the Chinese family. Furthermore, amniotic fluid was taken from the mother during the second trimester, and DNA was extracted to analyze the type of PKLR gene mutation. The proband received cord blood and bone marrow from the second child of the mother for hematopoietic stem cell transplantation and achieved normal hematopoiesis. The genetic characterization analysis and genotype-phenotype correlation study of PKLR gene suggested that NGS was an effective method to confirm the molecular diagnosis of intractable hemolytic anemia. The identification of the mutation aided in prenatal diagnosis in the second pregnancy and the effective clinical management of the affected family.


Assuntos
Anemia Hemolítica Congênita não Esferocítica/diagnóstico , Testes Genéticos/métodos , Piruvato Quinase/deficiência , Piruvato Quinase/genética , Erros Inatos do Metabolismo dos Piruvatos/diagnóstico , Anemia Hemolítica Congênita não Esferocítica/genética , Pré-Escolar , China , Feminino , Marcadores Genéticos , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Gravidez , Diagnóstico Pré-Natal/métodos , Erros Inatos do Metabolismo dos Piruvatos/genética
11.
Appl Microbiol Biotechnol ; 102(21): 9303-9316, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30073395

RESUMO

The specialty of gastroenterology will be affected profoundly by the ability to modify the gastrointestinal microbiota through the use of antibiotics. This study investigated the in vivo effect of roxithromycin on gut bacteria and gene expression of colonic epithelial cells (CECs) using microbial 16S rDNA and colonic epithelial cell RNA sequencing, respectively. The results showed that roxithromycin distinctly lowered the microbial diversity in both the small intestine and cecum and altered the compositions of bacteria at both the phylum and genus levels, including the reduction of some bacteria beneficial to the hosts' health. Eight decreased and 8 increased genera in the small intestine and 17 decreased and 4 increased genera of bacteria in the cecum were most affected by roxithromycin consumption. This consumption further altered the CECs' expression of multiple genes. Thirty-one genes, which were significantly enriched in seven KEGG pathways and related to immune response, wound healing, and fibrosis, were significantly affected. Roxithromycin ingestion in healthy hosts, therefore, might lead to some undesirable consequences via affecting hosts' gut microbiota and CECs. Our work offers a more comprehensive understanding of the impact of consuming roxithromycin on human health.


Assuntos
Bactérias/efeitos dos fármacos , Colo/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Roxitromicina/farmacologia , Animais , Antibacterianos/farmacologia , Ceco/efeitos dos fármacos , Ceco/microbiologia , Colo/microbiologia , DNA Bacteriano/genética , Células Epiteliais/microbiologia , Masculino , RNA Ribossômico 16S/genética , Ratos , Ratos Sprague-Dawley
12.
J Nanosci Nanotechnol ; 18(10): 6732-6739, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29954488

RESUMO

OBJECTIVE: Cisplatin has limited clinical applications due to drug resistance. PAMAM dendrimer was chosen as a vehicle to counteract cisplatin-resistance and its mechanism was assessed. METHODS: Generation 5 Polyamidoamine dendrimer (G5) was modified by glutaric anhydride (GA) and then conjugated with cisplatin. The cisplatin release of G5-GA-cisplatin was evaluated at pH 5.5 and pH 7.4. The cytotoxicity of G5-GA-cisplatin and free cisplatin was compared in cisplatin-resistant breast cancer cell line MCF-7R. The intracellular platinum content of MCF-7R was determined using ICP-MS. The expression of Ctr1 and ATP7B of MCF-7R cells was also evaluated. RESULTS: An average of 75 amino groups present in the G5 PAMAM surface were converted into glutaric acid (G5-GA75) and platinum loading was 350±21 µg per 1 mg of G5-GA75. G5-Ac75-cisplatin complex exhibited controlled release of cisplatin at different pH over a period of 96 h. After 96 h incubation with G5-Ac75-cisplatin, cell viability was 27.47±2.53%, 12.18±0.65% and 11.62±0.84% using platinum concentration of 1 µg/ml, 3 µg/ml and 5 µg/ml, respectively. Meanwhile, 46.33±5.06% cells survived even in the high platinum concentration of 5 µg/ml after 96 h incubation with free cisplatin. G5-GA75 led to 3-6 times higher cisplatin accumulation than free cisplatin in MCF-7R cells, because MCF-7R cells exhibited lower Ctr1 expression and higher ATP7B expression than MCF-7 cells. CONCLUSION: The G5-GA75-cisplatin complex displayed greater anticancer activity than free cisplatin in the cisplatin-resistant breast cancer cell line MCF-7R. The low levels of Ctr1 and high levels of ATP7B in MCF-7R caused G5-GA75 to allow the accumulation of cisplatin, which in turn increased the cytotoxicity. Results indicated that glutaryl G5 PAMAM may be a potential carrier for cisplatin targeting in breast cancer.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Cisplatino/administração & dosagem , Dendrímeros/química , Portadores de Fármacos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Cisplatino/farmacocinética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Glutaratos/química , Humanos , Células MCF-7
13.
Int J Mol Sci ; 18(3)2017 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-28335440

RESUMO

Polyphenol compositions and concentrations in skins and seeds of five muscadine grapes (cv. "Noble", "Alachua", "Carlos", "Fry", and "Granny Val") cultivated in the United States (Tallahassee-Florida, TA-FL) and South China (Nanning-Guangxi, NN-GX and Pu'er-Yunnan, PE-YN) were investigated, using ultra performance liquid chromatography tandem triple quadrupole time-of-flight mass spectrometry (UPLC Triple TOF MS/MS). Fourteen ellagitannins were newly identified in these muscadine grapes. The grapes grown in NN-GX accumulated higher levels of ellagic acid, methyl brevifolin carboxylate, and ellagic acid glucoside in skins, and penta-O-galloyl-glucose in seeds. In PE-YN, more flavonols were detected in skins, and higher contents of flavan-3-ols, ellagic acid, and methyl gallate were identified in seeds. Abundant seed gallic acid and flavonols were found among the grapes grown in TA-FL. Based on principal component analysis (PCA) of 54 evaluation parameters, various cultivars grown in different locations could be grouped together and vice versa for the same cultivar cultivated in different regions. This is the result of the interaction between genotype and environmental conditions, which apparently influences the polyphenol synthesis and accumulation.


Assuntos
Adaptação Fisiológica , Polifenóis/metabolismo , Vitis/química , Ácido Elágico/análise , Ácido Elágico/metabolismo , Flavonóis/análise , Flavonóis/metabolismo , Ácido Gálico/análise , Ácido Gálico/metabolismo , Variação Genética , Polifenóis/análise , Vitis/genética , Vitis/metabolismo
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(8): 945-949, 2017 Aug.
Artigo em Zh | MEDLINE | ID: mdl-28774373

RESUMO

Acute lymphoblastic leukemia (ALL) is the most common malignant hematological disease in childhood. Glucocorticoids are frequently used in the chemoradiotherapy regimen for ALL and can induce the apoptosis of ALL cells through several signaling pathways, but about 10% of ALL children have poor response to glucocorticoids. Studies have revealed that glucocorticoids induce the apoptosis of ALL cells by upregulating the expression of BIM gene, and BIM gene is associated with glucocorticoid resistance in childhood ALL. This article reviews the recent studies on glucocorticoid resistance in childhood ALL, especially the role of BIM and its expression products in this process.


Assuntos
Proteína 11 Semelhante a Bcl-2/genética , Glucocorticoides/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Apoptose , Criança , Resistência a Medicamentos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
15.
Ann Hematol ; 95(9): 1411-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27307280

RESUMO

Early mortality remains a major challenge for the treatment of hemophagocytic lymphohistiocytosis (HLH), which warrants the need for prompt risk stratification in the early phase of the disease. We retrospectively analyzed clinical features of a cohort of pediatric patients managed at a tertiary hospital in southern China from 2005 to 2015. A total of 116 patients (median age 27.5 months) with predominantly secondary HLH were included. In a multivariate Cox regression model, neutrophils <0.5 × 10(9)/L (risk ratio (RR) = 5.01; 95 % confidence interval (CI) 1.55-16.20; P = 0.007), total bilirubin over twofold upper limit of normal value (RR = 2.86; 95 % CI 0.83-9.88; P = 0.097), and albumin ≤20 g/L (RR = 5.79; 95 % CI 1.70-19.73; P = 0.005) at diagnosis were independent risk factors for 30-day mortality. The 30-day overall survival rate (OS) of patients with three risk factors was significantly lower than that of patients with zero to two risk factors (0 vs 90.7 %; P<0.001). Patients with three risk factors were 64-fold more likely to have early adverse outcome as compared to patients with zero to two risk factors (RR = 64.45; 95 % CI 18.35-226.33; P<0.001). Platelet count normalization in 2 weeks was an independent predictor for resolution after initial therapy with an odds ratio (OR) of 18.4 (95 % CI 2.7-122.9; P = 0.003). Our results indicate that severe neutropenia and liver function damage are prognostic factors for early death in HLH and platelet count normalization in 2 weeks is a critical predictor for resolution after initial therapy.


Assuntos
Linfo-Histiocitose Hemofagocítica/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adolescente , Bilirrubina/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Fígado/patologia , Fígado/fisiopatologia , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Análise Multivariada , Neutropenia/sangue , Contagem de Plaquetas , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise , Taxa de Sobrevida , Fatores de Tempo
16.
J Pediatr Hematol Oncol ; 37(3): e138-42, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25222059

RESUMO

CD20 is a B-cell differentiation antigen that is expressed variably in precursor B-cell acute lymphoblastic leukemia (BCP-ALL). The prognostic significance of CD20 expression in childhood BCP-ALL remains controversial. Some studies have demonstrated that CD20 overexpression correlates with worse survival in pediatric patients with BCP-ALL, but some other studies suggest a better outcome. To explore the prognostic role of high CD20 expression in pediatric BCP-ALL, we performed a meta-analysis of the previous studies that provided survival information according to CD20 expression status. Pooled hazard ratios (HRs) indicated that high CD20 expression had no inferior impact on the prognosis of pediatric BCP-ALL. The summary HR for overall survival was 0.70 and combined HR for event-free survival was 1.01. These findings suggest that high CD20 expression does not influence the outcome for pediatric BCP-ALL. CD20 may lack prognostic value in children with BCP-ALL.


Assuntos
Antígenos CD20/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Doença Aguda , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Prognóstico
17.
Brain Inj ; 29(10): 1239-1245, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26083053

RESUMO

OBJECTIVE: Resolution of a traumatic acute subdural haematoma (ASDH) requires weeks or months. However, cases of rapid spontaneous resolution of ASDH within 72 hours after trauma have been reported. The purpose of this study was to obtain a better understanding of the clinical and CT features of cases of rapid resolution following traumatic ASDH. METHOD: Between 2011-2014, the authors retrospectively collected data from 14 patients with rapid resolution of traumatic ASDH. The clinical data and CT findings of these cases were collected and analysed. RESULTS: In 13 of the 14 patients, there was a rapid spontaneous resolution of the ASDH within 48 hours. The mean haematoma width of the second CT was significantly smaller than the width of the initial CT. A significantly marked resolution of the midline shift was observed in the second CT in all patients. The outcome was good in the majority of patients. CONCLUSIONS: The acute fluctuation of ICP may drive the spontaneous rapid resolution and redistribution of ASDH. Patients with abnormal coagulant function may be more likely to experience rapid resolution of ASDH. A band of low density in the initial CT image may be a useful sign for rapid resolution of ASDH.

18.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(9): 971-4, 2015 Sep.
Artigo em Zh | MEDLINE | ID: mdl-26412181

RESUMO

OBJECTIVE: To summarize the clinical features of sinusoidal obstruction syndrome (SOS) and to improve the understanding of this disease. METHODS: A retrospective study was performed on the clinical data of 12 children with SOS including clinical manifestations, laboratory results, imaging findings, treatment, and prognosis. RESULTS: Of the 12 cases, 8 were secondary to acute lymphoblastic leukemia, and 4 had undergone hematopoietic stem cell transplantation. Manifestations mainly included abdominal distention (4 cases), hepatomegaly with tenderness (9 cases), splenomegaly (6 cases), and weight increase (10 cases). Biochemical tests revealed varying degrees of liver damage in all cases. In the coagulation function test, the activated partial thromboplastin time (APTT) was prolonged in 7 cases. Out of the 7 patients who underwent serum D-dimer test, 4 showed elevated serum level of D-dimer. In routine blood tests, 4 cases showed decreases in both white blood cells and neutrophils. In addition, varying degrees of thrombocytopenia were observed in 9 cases. Eight patients were subjected to color Doppler ultrasound examination, and diffuse hepatomegaly, inhomogeneous liver parenchyma, unclear or thinner hepatic veins, hydrothorax/ascites, or splenomegaly was observed. Sinusoidal dilatation or hepatic cell infiltration was observed in 2 patients who underwent liver biopsy. Treatments were basically symptomatic and supportive therapies, and the prognosis was good in all patients. CONCLUSIONS: SOS should be considered in children who present with hepatomegaly, sudden weight gain, liver dysfunction and coagulation dysfunction after they have received chemotherapy for leukemia and hematopoietic stem cell transplantation.


Assuntos
Hepatopatia Veno-Oclusiva/terapia , Criança , Pré-Escolar , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hepatopatia Veno-Oclusiva/sangue , Humanos , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(2): 164-7, 2015 Feb.
Artigo em Zh | MEDLINE | ID: mdl-25760842

RESUMO

OBJECTIVE: To investigate the association between rs1799864 single nucleotide polymorphism (SNP) of the C-C chemokine receptor 2 (CCR2) gene and susceptibility of hemophagocytic lymphohistiocytosis (HLH) in children. METHODS: The clinical and laboratory data of 86 children diagnosed with HLH between January 2007 and December 2013 were retrospectively reviewed. The CCR2 gene rs1799864 was genotyped by SNaPshot technique in 86 HLH children and 128 healthy controls. The genotypic and allelic frequencies in the two groups were comparatively analyzed. RESULTS: No significant difference either in genotypic or allelic frequencies of rs1799864 polymorphism of the CCR2 gene was observed between HLH patients and controls (P>0.05), but there were significant differences in the age of onset and the periods of temperature and platelet returning to normal after treatment (P<0.05). CONCLUSIONS: There is no association between CCR2 gene rs1799864 polymorphism and the risk for HLH in children. However, the genotypic differences of this polymorphism might be associated with clinical characteristics and prognosis of HLH.


Assuntos
Linfo-Histiocitose Hemofagocítica/genética , Polimorfismo de Nucleotídeo Único , Receptores CCR2/genética , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Masculino
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(7): 677-82, 2015 Jul.
Artigo em Zh | MEDLINE | ID: mdl-26182270

RESUMO

OBJECTIVE: To investigate frequency distribution of gene polymorphisms of PRF1 gene in children with hemophagocytic lymphohistiocytosis (HLH), and to explore whether the possible gene polymorphisms of PRF1 gene confer an increased risk of susceptibility to HLH. METHODS: Forty-eight children who were diagnosed with HLH between January 2009 and December 2013 (HLH group) and 100 healthy children (control group) were enrolled in this study. The gene polymorphisms in the coding region of PRF1 gene, which consists of three exons and two introns, were genotyped by PCR, followed by direct sequencing. RESULTS: Three single nucleotide polymorphisms (SNPs) were revealed in the coding sequence of PRF1 in the 48 children with HLH. Seven SNPs were detected in the noncoding sequence. Other two SNPs in the noncoding sequence including rs10999426 and rs10999427 were detected only in 5 healthy children (5%). There was no significant difference in allelic frequencies of all the SNPs above between the HLH and control groups (P>0.05). Haplotype analysis showed there was a pair-wise linkage disequilibrium between rs10999426 and rs10999427 (D=1, r2=1), but there was no significant difference in the distribution of A-T haplotype between the HLH and control groups (P>0.05). CONCLUSIONS: There is no association between gene polymorphisms of PRF1 gene and the susceptibility to HLH. There is a pair-wise linkage disequilibrium between rs10999426 and rs10999427, but a low detection rate of A-T haplotype in healthy children indicates that it might not play a protective role in the development of HLH.


Assuntos
Linfo-Histiocitose Hemofagocítica/genética , Perforina/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Criança , Pré-Escolar , Feminino , Haplótipos , Humanos , Lactente , Desequilíbrio de Ligação , Masculino
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