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1.
Chem Commun (Camb) ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32289815

RESUMO

Anisotropic films composed of aligned CsPbBr3 nanowires (NWs) have been successfully fabricated using a mechanical rubbing method. The films with a dense and uniform morphology show polarization photoluminescence (PL) behavior. Combined with an optimal device structure, a polarized light-emitting diode (LED) with a turn-on voltage as low as 6.5 V was obtained.

2.
Cancer Lett ; 483: 66-74, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32142917

RESUMO

Endometrial cancer, a type of primary epithelial malignant tumor in the endometrium, is one of the three most common malignant tumors of the female reproductive system. While the incidence of endometrial cancer has been recently rising, its etiology remains unclear. In this study we found that EM2D9, an independently developed monoclonal antibody, specifically recognized endometrial cancer cells; we further determined that EM2D9 target protein was α5ß1. In vitro and in vivo experiments showed that EM2D9 inhibited the migration of endometrial cancer cells. Real-time quantitative PCR results showed that the expression of CD151 mRNA in endometrial carcinoma cells significantly decreased after EM2D9 treatment. We also found that EM2D9 affected the FAK signaling pathway. Collectively, these results shed light on a new mechanism for the development of endometrial carcinoma.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31651418

RESUMO

The clinical presentation in Chinese patients with sporadic Creutzfeldt-Jakob disease (sCJD) may be unique due to the big difference in the codon 129 polymorphism of the prion protein gene (PRNP). This study retrospectively reviewed 26 cases of sCJD diagnosed in a single center in recent years. All 26 sCJD patients received brain magnetic resonance imaging scan, cerebrospinal fluid 14-3-3 protein detection, electroencephalogram, and PRNP gene screening. The codon 129 polymorphism were all homozygous MM in 26 sCJD patients. The main onset symptoms of sCJD patients were rapidly progressive dementia, visual impairment, and cerebellar ataxia. At the time of diagnosis, the incidence of myoclonus and akinetic mutism were relatively low (<50%). For auxiliary examinations, the positive rate of the typical magnetic resonance imaging (MRI) abnormalities, cerebrospinal fluid 14-3-3 protein, and electroencephalogram-periodic sharp wave complex was 96%, 64%, and 50%, respectively. As MM genotype is dominant and brain MRI is sensitive, brain MRI seems to play a major role in diagnosis of sCJD in Chinese.

4.
Mol Ther Methods Clin Dev ; 15: 9-17, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31534983

RESUMO

HIV infection induces a robust T cell response that is sustained by high viremia, but falls following the onset of antiretroviral therapy (ART). Relatively little has been reported on the subsequent stability of the HIV-specific T cell response in individuals on durable therapy. Such data are critical for powering clinical trials testing T cell-based immunotherapies. In a cross-sectional study, HIV-specific T cell responses were detectable by ex vivo interferon (IFN)-γ ELISpot (average ∼1,100 spot-forming units [SFUs]/106 peripheral blood mononuclear cells) in persons living with HIV (PLWH; n = 34), despite median durable ART suppression of 5.0 years. No substantial association was detected between the summed HIV-specific T cell response and the size of the replication-competent HIV reservoir. T cell responses were next measured in participants sampled weekly, monthly, or yearly. HIV-specific T cell responses were highly stable over the time periods examined; within-individual variation ranged from 16% coefficient of variation (CV) for weekly to 27% CV for yearly sampling. These data were used to generate power calculations for future immunotherapy studies. The stability of the HIV-specific T cell response in suppressed PLWH will enable powered studies of small sizes (e.g., n = 6-12), facilitating rapid and iterative testing for T cell-based immunotherapies against HIV.

5.
Cancer Manag Res ; 11: 5777-5783, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417316

RESUMO

Purpose: Radical prostatectomy (RP) is a common treatment for prostate cancer, but a fraction of patients may experience PSA recurrence after surgery, manifesting as an elevation in prostate specific antigen (PSA). Vast literature has reported different prognostic factors for PSA recurrence without reaching a consensus. This retrospective study investigated the efficacy of a new indicator in predicting PSA recurrence in patients after RP. Patients and methods: From October 2000 to December 2015, 102 PCa patients who underwent laparoscopic prostatectomy in the Urology Department of Peking Union Medical College Hospital were analyzed. We calculated PSApostd3/PSApre, defined as the ratio of the PSA on day 3 postop as the numerator and the pre-operative PSA as the denominator, in these patients to represent PSA decrement after surgery, and investigated its relationship with PSA recurrence during follow-up. Results: The receiver operating characteristic (ROC) curve of PSApostd3/PSApre derived a cut-off at 0.453 (sensitivity=0.704, specificity=0.853, P<0.0001), suggesting an increased risk of PSA recurrence in patients whose PSA on day 3 postop did not decrease to approximately half of their preoperative levels. Among several factors, PSApostd3/PSApre (P<0.0001), pathological T stage (P=0.042) and Gleason Grade (P=0.021) were determined to be significantly associated with PSA recurrence by Fisher's exact test, while only PSApostd3/PSApre (P<0.001) was significantly related to PSA recurrence-free survival (PRFS) by multivariate logistic regression analysis. Conclusion: These results imply that PSApostd3/PSApre could provide substantial information for PSA recurrence prediction in patients after RP.

6.
Nat Biotechnol ; 37(10): 1163-1173, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31451733

RESUMO

A major limitation of current humanized mouse models is that they primarily enable the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types, including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, which contains up to 40 cell types, including nonhematopoietic cells, into immunodeficient mice (lung-only mice) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus humanized mice, lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T-cell responses following cytomegalovirus infection that control virus replication. Lung-only mice and bone marrow/liver/thymus-lung humanized mice substantially increase the number of human pathogens that can be studied in vivo, facilitating the in vivo testing of therapeutics.


Assuntos
Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Pulmão/fisiologia , Infecção por Zika virus/virologia , Animais , Anticorpos Antivirais , Células Apresentadoras de Antígenos , Infecções por Coronavirus/imunologia , Citocinas/genética , Citocinas/metabolismo , Citomegalovirus/fisiologia , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos SCID , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Tropismo/imunologia , Replicação Viral , Zika virus/imunologia , Infecção por Zika virus/imunologia
7.
Front Neurol ; 10: 547, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178822

RESUMO

Cerebral amyloid angiopathy (CAA)-related inflammation (CAA-RI) is a rare CAA variant characterized by acute or subacute encephalopathy, headache, epilepsy, or focal neurological deficits. Radiologically, CAA-RI presents with widespread white matter lesions on brain magnetic resonance imaging (MRI) in addition to the hemorrhagic imaging features of CAA. Previous studies have found that the apolipoprotein E (ApoE) ε4 allele and ε4/ε4 genotype were over-represented in CAA-RI. The role of the ApoE ε2 allele in CAA-RI, however, is largely unknown, partly due to the rarity of the ε2/ε2 genotype in the general population. The authors report the first case of CAA-RI with the rare ApoE ε2/ε2 genotype. The patient presented with mild clinical symptoms but striking neuroimaging abnormalities. The response to small-dose glucocorticoids was satisfactory. Because ApoE ε2 promotes amyloid ß accumulation and fibrinoid necrosis in the cerebral vasculature, the ε2/ε2 genotype, similar to ε4/ε4, may also be a precipitating factor for CAA-RI. To clarify the role of ApoE ε2 in CAA-RI, studies with large sample sizes investigating whether ε2 is more common in patients with CAA-RI than in those with CAA only are warranted.

8.
Chin Med J (Engl) ; 131(24): 2904-2909, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30539901

RESUMO

Background: Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonance imaging (MRI) in the disease progression of ALS. Methods: From September 2015 to March 2017, ten patients diagnosed with ALS in Peking Union Medical College Hospital completed head MRI scans at baseline and during follow-up. Multimodal MRI analyses, including gray matter (GM) volume measured by voxel-based morphometry; cerebral blood flow (CBF) evaluated by arterial spin labeling; functional connectivity, including low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), measured by resting-state functional MRI; and integrity of white-matter (WM) fiber tracts evaluated by diffusion tensor imaging, were performed in these patients. Comparisons of imaging metrics were made between baseline and follow-up using paired t-test. Results: In the longitudinal comparisons, the brain structure (GM volume of the right precentral gyri, left postcentral gyri, and right thalami) and perfusion (CBF of the bilateral temporal poles, left precentral gyri, postcentral gyri, and right middle temporal gyri) in both motor and extramotor areas at follow-up were impaired to different extents when compared with those at baseline (all P < 0.05, false discovery rate adjusted). Functional connectivity was increased in the motor areas (fALFF of the right precentral gyri and superior frontal gyri, and ReHo of right precentral gyri) and decreased in the extramotor areas (fALFF of the bilateral middle frontal gyri and ReHo of the right precuneus and cingulate gyri) (all P < 0.001, unadjusted). No significant changes were detected in terms of brain WM measures. Conclusion: Multimodal MRI could be used to monitor short-term brain changes in ALS patients.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Adulto , Esclerose Amiotrófica Lateral/fisiopatologia , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Medicine (Baltimore) ; 97(38): e12495, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30235754

RESUMO

To compare the accuracy of magnetic resonance-guided prostate biopsy (MR-GPB) and template-guided transperineal prostate saturation biopsy (TTPSB).A total of 219 patients with elevated prostate-specific antigen, abnormal digital rectal examination or ultrasound findings were enrolled. All patients underwent multiparametric magnetic resonance image (mpMRI). Patients with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 to 5 underwent MR-GPB using 2 to 5 biopsy cores and then immediately underwent an 11-region TTPSB. Patients with a PI-RADS score of 1 to 2 underwent TTPSB alone. We compared the detection rates for any cancer, clinically significant prostate cancer (csPCA), and the spatial distribution of missed csPCA lesions.Among the 219 cases, 66 (30.1%) had a PI-RADS score of 1 to 2 on mpMRI. The detection rate of TTPSB in these patients was 9.1% (6/66). In total, detection rates for any cancer and csPCA were 48.9% (107/219) and 42.9% (94/219), respectively. Detection rates for any cancer (TTPSB 87/219, 39.7%; MR-GPB76/219, 34.7%, P = .161) and csPCA (TTPSB 76/219, 34.7%; MR-GPB 72/219, 32.9%, P = .636) did not significantly differ between the 2 groups. The csPCA lesions missed by MR-GPB were most commonly located on the left (8.5%, 8/94) and right (9.6%, 9/94) sides of the urethra.MR-GPB can reduce the rate of unnecessary prostate biopsies by approximately 30% and exhibits an efficacy comparable to TTPSB for the detection of any cancer and csPCA. Nevertheless, approximately 1/4 of csPCAs were missed by MR-GPB and were most commonly located on both sides of the urethra.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Biópsia Guiada por Imagem/estatística & dados numéricos , Imagem por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Períneo/patologia , Próstata/diagnóstico por imagem , Próstata/patologia , Uretra/patologia
10.
BMJ Open ; 8(6): e021964, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29934393

RESUMO

INTRODUCTION: Paraquat (PQ) is a widely used herbicide which is inexpensive and easily accessible for people in rural areas. A small amount of PQ ingestion could be lethal, yet currently, the optimal treatment is still controversial. Extracorporeal therapies (ECTR) have been practised in PQ poisoning management, though limited evidence could be obtained to suggest its superiority over conservative therapy. Haemodialysis (HD) and haemoperfusion (HP) are most commonly used, while some institutions also choose HP-HD concurrent therapy. The object of the present trial is to investigate whether haemopurification therapy can reduce mortality compared with conservative therapy. METHODS AND ANALYSIS: This is a planned single-centre, non-blinded, randomised controlled trial. Acute PQ poisoned adults who have orally ingested PQ within 24 hours would be recruited. A total of 360 patients would be recruited and randomly assigned to four groups, that is, HP, HD, concurrent HP-HD and control, at a 1:1:1:1 ratio. Subjects would be also stratified by their urine dithionite test results. Primary outcome is 28-day all-cause mortality. Secondary outcomes include survival time, all-cause mortality at the 3rd, 7th and 60th day, rate of major complications, Acute Physiologic and Chronic Health Evaluation score and Poisoning Severity Score, etc. ETHICS AND DISSEMINATION: The protocol and informed consent documents have been approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University in September 2017 (approval number: 2017-KY-10). The result of this trial would be submitted to peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03314909; Pre-results.


Assuntos
Hemoperfusão , Herbicidas/envenenamento , Paraquat/envenenamento , Envenenamento/terapia , China/epidemiologia , Humanos , Envenenamento/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Fatores de Tempo
11.
Front Neurol ; 9: 364, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29881369

RESUMO

Objective: To characterize the patterns of brain atrophy and perfusion as measured by arterial spin labeling (ASL)-MRI, in amyotrophic lateral sclerosis (ALS) patients with varying levels of cognitive deficit, including ALS with frontotemporal dementia (FTD). Methods: A total of 55 ALS patients and 20 healthy controls (HCs) were included, and all participants underwent neuropsychological assessments and MRI scans. According to their cognitive performance, ALS patients were further subclassified into ALS with normal cognition (ALS-Cn, n = 27), ALS with cognitive impairment (ALS-Ci, n = 17), and ALS-FTD (n = 11). Voxel-based comparisons of gray matter (GM) changes and cerebral blood flow (CBF) were conducted among the subgroups. Results: The whole-brain comparisons of GM changes and CBF among ALS-Ci, ALS-Cn, and HCs were not significantly different. However, the ALS-FTD patients demonstrated a similar pattern of GM loss and hypoperfusion with more significant alterations in the left frontal and temporal lobe compared with the HCs, ALS-Cn, and ALS-Ci patients. Decreased CBF was found in many of the same brain areas wherein structural alterations occurred, although isolated GM loss and hypoperfusion were also observed. In addition, for both GM and CBF abnormalities, a similar pattern of changes was found in the comparisons of ALS-FTD vs. ALS-Ci, ALS-FTD vs. ALS-Cn, and ALS-FTD vs. HCs, with the differences being most significant between ALS-FTD and HCs. Conclusion: The cognitive status of ALS patients is associated with different patterns of GM changes and cerebral perfusion. ASL-MRI might be a useful tool with which to investigate the pathological burden of ALS and to disclose the early signature of possible cognitive impairment.

12.
Blood ; 131(14): 1576-1586, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29437595

RESUMO

Juvenile myelomonocytic leukemia (JMML), a rare and aggressive myelodysplastic/myeloproliferative neoplasm that occurs in infants and during early childhood, is characterized by excessive myelomonocytic cell proliferation. More than 80% of patients harbor germ line and somatic mutations in RAS pathway genes (eg, PTPN11, NF1, NRAS, KRAS, and CBL), and previous studies have identified several biomarkers associated with poor prognosis. However, the molecular pathogenesis of 10% to 20% of patients and the relationships among these biomarkers have not been well defined. To address these issues, we performed an integrated molecular analysis of samples from 150 JMML patients. RNA-sequencing identified ALK/ROS1 tyrosine kinase fusions (DCTN1-ALK, RANBP2-ALK, and TBL1XR1-ROS1) in 3 of 16 patients (18%) who lacked canonical RAS pathway mutations. Crizotinib, an ALK/ROS1 inhibitor, markedly suppressed ALK/ROS1 fusion-positive JMML cell proliferation in vitro. Therefore, we administered crizotinib to a chemotherapy-resistant patient with the RANBP2-ALK fusion who subsequently achieved complete molecular remission. In addition, crizotinib also suppressed proliferation of JMML cells with canonical RAS pathway mutations. Genome-wide methylation analysis identified a hypermethylation profile resembling that of acute myeloid leukemia (AML), which correlated significantly with genetic markers with poor outcomes such as PTPN11/NF1 gene mutations, 2 or more genetic mutations, an AML-type expression profile, and LIN28B expression. In summary, we identified recurrent activated ALK/ROS1 fusions in JMML patients without canonical RAS pathway gene mutations and revealed the relationships among biomarkers for JMML. Crizotinib is a promising candidate drug for the treatment of JMML, particularly in patients with ALK/ROS1 fusions.


Assuntos
Proliferação de Células , Crizotinibe/farmacologia , Perfilação da Expressão Gênica , Leucemia Mielomonocítica Juvenil/genética , Leucemia Mielomonocítica Juvenil/metabolismo , Mutação , Proteínas de Fusão Oncogênica , Inibidores de Proteínas Quinases/farmacologia , Adolescente , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Criança , Pré-Escolar , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lactente , Leucemia Mielomonocítica Juvenil/tratamento farmacológico , Masculino , Proteínas de Fusão Oncogênica/biossíntese , Proteínas de Fusão Oncogênica/genética
13.
Cell Cycle ; 16(22): 2204-2211, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28727484

RESUMO

Liver cancer is the sixth most prevalent cancer, and the third most frequent cause of cancer-related deaths. Circular RNAs (circRNAs), a kind of special endogenous ncRNAs, have been coming back to the forefront of cancer genomics research. In this study, we used a systems biology approach to construct and analyze the circRNA molecular regulatory networks in the context of liver cancer. We detected a total of 127 differentially expressed circRNAs and 3,235 differentially expressed mRNAs. We selected the top-5 upregulated circRNAs to construct a circRNA-miRNA-mRNA network. We enriched the pathways and gene ontology items and determined their participation in cancer-related pathways such as p53 signaling pathway and pathways involved in angiogenesis and cell cycle. Quantitative real-time PCR was performed to verify the top-five circRNAs. ROC analysis showed circZFR, circFUT8, circIPO11 could significantly distinguish the cancer samples, with an AUC of 0.7069, 0.7575, and 0.7103, respectively. Our results suggest the circRNA-miRNA-mRNA network may help us further understand the molecular mechanisms of tumor progression in liver cancer, and reveal novel biomarkers and therapeutic targets.


Assuntos
Neoplasias Hepáticas/genética , RNA/genética , Humanos , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , Biologia de Sistemas/métodos
14.
J Clin Invest ; 127(8): 3126-3135, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28714868

RESUMO

BACKGROUND: The histone deacetylase (HDAC) inhibitor vorinostat (VOR) can increase HIV RNA expression in vivo within resting CD4+ T cells of aviremic HIV+ individuals. However, while studies of VOR or other HDAC inhibitors have reported reversal of latency, none has demonstrated clearance of latent infection. We sought to identify the optimal dosing of VOR for effective serial reversal of HIV latency. METHODS: In a study of 16 HIV-infected, aviremic individuals, we measured resting CD4+ T cell-associated HIV RNA ex vivo and in vivo following a single exposure to VOR, and then in vivo after a pair of doses separated by 48 or 72 hours, and finally following a series of 10 doses given at 72-hour intervals. RESULTS: Serial VOR exposures separated by 72 hours most often resulted in an increase in cell-associated HIV RNA within circulating resting CD4+ T cells. VOR was well tolerated by all participants. However, despite serial reversal of latency over 1 month of VOR dosing, we did not observe a measurable decrease (>0.3 log10) in the frequency of latent infection within resting CD4+ T cells. CONCLUSIONS: These findings outline parameters for the experimental use of VOR to clear latent infection. Latency reversal can be achieved by VOR safely and repeatedly, but effective depletion of persistent HIV infection will require additional advances. In addition to improvements in latency reversal, these advances may include the sustained induction of potent antiviral immune responses capable of recognizing and clearing the rare cells in which HIV latency has been reversed. TRIAL REGISTRATION: Clinicaltrials.gov NCT01319383. FUNDING: NIH grants U01 AI095052, AI50410, and P30 CA016086 and National Center for Advancing Translational Sciences grant KL2 TR001109.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Esquema de Medicação , Infecções por HIV/tratamento farmacológico , Inibidores de Histona Desacetilases/administração & dosagem , Ácidos Hidroxâmicos/administração & dosagem , Latência Viral/efeitos dos fármacos , Adulto , Idoso , Fármacos Anti-HIV/farmacologia , Feminino , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Fatores de Tempo , Resultado do Tratamento , Ativação Viral , Vorinostat
15.
Genet Med ; 19(7): 796-802, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28102861

RESUMO

PURPOSE: Precise genetic diagnosis of inherited bone marrow failure syndromes (IBMFS), a heterogeneous group of genetic disorders, is challenging but essential for precise clinical decision making. METHODS: We analyzed 121 IBMFS patients using a targeted sequencing covering 184 associated genes and 250 IBMFS patients using whole-exome sequencing (WES). RESULTS: We achieved successful genetic diagnoses for 53 of 121 patients (44%) using targeted sequencing and for 68 of 250 patients (27%) using WES. In the majority of cases (targeted sequencing: 45/53, 85%; WES: 63/68, 93%), the detected variants were concordant with, and therefore supported, the clinical diagnoses. However, in the remaining 13 cases (8 patients by target sequencing and 5 patients by WES), the clinical diagnoses were incompatible with the detected variants. CONCLUSION: Our approach utilizing targeted sequencing and WES achieved satisfactory diagnostic rates and supported the efficacy of massive parallel sequencing as a diagnostic tool for IBMFS.Genet Med advance online publication 19 January 2017.


Assuntos
Anemia Aplástica/diagnóstico , Anemia Aplástica/genética , Doenças da Medula Óssea/diagnóstico , Doenças da Medula Óssea/genética , Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/genética , Sequenciamento de Nucleotídeos em Larga Escala/estatística & dados numéricos , Exoma/genética , Feminino , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Mutação/genética , Análise de Sequência de DNA/métodos , Sequenciamento Completo do Exoma/métodos
16.
J Cell Physiol ; 232(9): 2581-2589, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27770612

RESUMO

Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated. In vitro, let-7i mimics suppressed the autophagic activities in human HTR-8/SVneo trophoblast cell line (HTR-8) and human placental choriocarcinoma cell line JEG-3, whereas let-7i inhibitor enhanced the activities. As a potential target of let-7i, autophagy-related 4B cysteine peptidase (Atg4B) had an increased expression level in SPE. As expected, the increased expression of Atg4B was negatively regulated by let-7i using dual luciferase reporter assay. Furthermore, these trophoblast-like cells transfected with the let-7i mimic or inhibitors resulted in a significant change of Atg4B in both mRNA and protein level. More importantly, Atg4B overexpression could partly reverse let-7i mimic-reduced LC3II/I levels; whereas Atg4B silencing partly attenuated let-7i inhibitor-induced the level of LC3II/I expression. Taken together, these findings suggest that let-7i is able to regulate autophagic activity via regulating Atg4B expression, which might contribute to the pathogenesis of PE. J. Cell. Physiol. 232: 2581-2589, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Autofagia , Cisteína Endopeptidases/metabolismo , MicroRNAs/metabolismo , Pré-Eclâmpsia/metabolismo , Trofoblastos/metabolismo , Adulto , Proteínas Relacionadas à Autofagia/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Cisteína Endopeptidases/genética , Regulação para Baixo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Gravidez , Interferência de RNA , Transdução de Sinais , Transfecção , Trofoblastos/patologia
17.
Oncotarget ; 8(63): 106296-106310, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29290949

RESUMO

Neurocan (NCAN), a secreted chondroitin sulfate proteoglycan, is one of the major inhibitory molecules for axon regeneration in nervous injury. However, its role in cancer is not clear. Here we observed that high NCAN expression was closely associated with the unfavorable outcome of neuroblastoma (NB). NCAN was also highly and ubiquitously expressed in the early lesions and terminal tumor of TH-MYCN mice, a NB model. Interestingly, exogenous NCAN (i.e., overexpression, recombinant protein and conditioned medium) transformed adherent NB cells into spheres whose malignancies in vitro (anchorage-independent growth and chemoresistance) and in vivo (xenograft tumor growth) were potentiated. Both chondroitin sulfate sugar chains and NCAN's core protein were essential for the sphere formation. The CSG3 domain was essential in the moiety of NCAN. Our comprehensive microarray analysis and RT-qPCR of mRNA expression suggested that NCAN treatment promoted cell division, and urged cells to undifferentiated state. The knockdown of NCAN in tumor sphere cells cultured from TH-MYCN mice resulted in growth suppression in vitro and in vivo. Our findings suggest that NCAN, which stimulates NB cells to promote malignant phenotypes, is an extracellular molecule providing a growth advantage to cancer cells.

18.
Br J Haematol ; 176(2): 248-257, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27861730

RESUMO

We assessed the clinical utility of next-generation sequencing (NGS)-based monitoring of minimal residual disease (MRD) in a uniformly treated cohort of 79 patients with paediatric B-cell acute lymphoblastic leukaemia. Bone marrow samples were collected at the time of diagnosis, days 33 and 80, pre- (4-5 months) and post- (24 months) maintenance therapy time points, and at relapse. We identified leukaemia-specific CDR3 sequences in 72 of 79 patients (91%) and detected MRD in 59 of 232 samples. Although MRD was detected in 28 of 55 samples (51%) on day 33, the frequencies of MRD detection decreased to 25% (16/65) at day 80, 19% (11/58) at 4-5 months and 7·4% (4/54) at 24 months. In a univariate analysis, positive MRD results on day 80 [relative risk (RR) 95% confidence interval (CI) = 7·438 (2·561-21·6), P < 0·001], at 4-5 months [RR (95% CI) = 10·24 (3·374-31·06), P < 0·001], and at 24 months [RR (95% CI) = 19·26 (4·974-74·59), P < 0·001] exhibited statistically significant associations with inferior leukaemia-free survival; this was confirmed using a Cox proportional hazard model. Our study suggests the promising potential of NGS-MRD for patients with B-cell ALL.


Assuntos
DNA de Neoplasias , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Linfócitos B/patologia , Exame de Medula Óssea , Criança , Pré-Escolar , DNA de Neoplasias/análise , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Análise de Sequência de DNA , Fatores de Tempo
20.
Adv Exp Med Biol ; 904: 1-22, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26900059

RESUMO

For the past century, scientists have developed a variety of methods to evaluate itch and pain in both animal models and human subjects to throw light on some of the most important pathways mediating these unpleasant sensations. Discoveries in the mechanisms underlying itch and pain in both physiological and pathological conditions relied greatly upon these studies and may eventually lead to the discovery of new therapeutics. However, it was a much more complicated job to access itch and pain in animal models than in human subjects due to the subjective nature of these sensations. The results could be contradictory or even misleading when applying different methodologies in animal models, especially under pathological conditions with a mixed sensation of itch and pain. This chapter introduces and evaluates some of the classical and newly designed methodologies to access the sensation of itch and pain in animal models as well as human subjects.


Assuntos
Camundongos/fisiologia , Modelos Animais , Nociceptividade/fisiologia , Dor/fisiopatologia , Prurido/fisiopatologia , Ratos/fisiologia , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Antipruriginosos/farmacologia , Antipruriginosos/uso terapêutico , Aprendizagem da Esquiva , Capsaicina/toxicidade , Condicionamento Clássico , Emoções , Histamina/toxicidade , Antagonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Camundongos/psicologia , Experimentação Humana não Terapêutica , Especificidade de Órgãos , Dor/tratamento farmacológico , Dor/etiologia , Dor/psicologia , Medição da Dor/métodos , Estimulação Física/efeitos adversos , Prurido/tratamento farmacológico , Prurido/etiologia , Prurido/psicologia , Ratos/psicologia , Especificidade da Espécie
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