Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Clin Invest ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31961825

RESUMO

Despite the effective clinical use of steroids for the treatment of Diamond Blackfan anemia (DBA), the mechanistic bases via which glucocorticoids regulate human erythropoiesis remain poorly understood. Here, we report that the sensitivity of erythroid differentiation to dexamethasone (Dex) is dependent on the developmental origin of human CD34+ progenitor cells, specifically increasing the expansion of CD34+ progenitors from peripheral blood (PB) but not cord blood (CB). Dexamethasone treatment of erythroid-differentiated PB, but not CB, CD34+ progenitors resulted in the expansion of a novel CD34+CD36+CD71hiCD105med immature colony-forming unit-erythroid (CFU-E) population. Furthermore, proteomics analyses revealed the induction of distinct proteins in dexamethasone-treated PB and CB erythroid progenitors. Dexamethasone treatment of PB progenitors resulted in the specific upregulation of p57Kip2, a Cip/Kip cyclin-dependent kinase inhibitor, and we identified this induction as critical; shRNA-mediated downregulation of p57Kip2, but not the related p27Kip1, significantly attenuated the impact of dexamethasone on erythroid differentiation and inhibited the expansion of the immature CFU-E subset. Notably, in the context of DBA, we found that steroid resistance was associated with a dysregulated p57Kip2 expression. Altogether, these data identify a novel glucocorticoid-responsive human erythroid progenitor and provide new insights into glucocorticoid-based therapeutic strategies for the treatment of patients with DBA.

2.
Biomacromolecules ; 20(11): 4230-4240, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31633916

RESUMO

Hyperbranched polysiloxane (HBPSi) is attracting increasing attention due to its intrinsic fluorescence and good biocompatibility. However, it is very challenging to explore its biological applications because of the low fluorescence intensity and quantum yield. Herein, we introduced rigid ß-cyclodextrin to the end of flexible polysiloxane chain to synthesize a novel fluorescent polymer (HBPSi-CD) and explore its biological applications. Results showed that the fluorescence intensity and quantum yield of HBPSi-CD, compared with HBPSi, were significantly enhanced. Theoretical calculations and transmission electron microscopy demonstrated that the synergy effect of intra/intermolecular hydrogen bonds and hydrophobic effect promoted the formation of large supramolecular self-assemblies and space electron delocalization systems, leading to intense fluorescence. Notably, the biocompatible HBPSi-CD not only lighted up mouse fibroblast cells, but also possessed high ibuprofen loading capacity (160 mg g-1) and superior pH-responsive drug release performance. This work promoted the development of biological applications of HBPSi.

3.
Cell Rep ; 28(11): 2996-3009.e7, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509757

RESUMO

Mammalian erythropoiesis yields a highly specialized cell type, the mature erythrocyte, evolved to meet the organismal needs of increased oxygen-carrying capacity. To better understand the regulation of erythropoiesis, we performed genome-wide studies of chromatin accessibility, DNA methylation, and transcriptomics using a recently developed strategy to obtain highly purified populations of primary human erythroid cells. The integration of gene expression, DNA methylation, and chromatin state dynamics reveals that stage-specific gene regulation during erythropoiesis is a stepwise and hierarchical process involving many cis-regulatory elements. Erythroid-specific, nonpromoter sites of chromatin accessibility are linked to erythroid cell phenotypic variation and inherited disease. Comparative analyses of stage-specific chromatin accessibility indicate that there is limited early chromatin priming of erythroid genes during hematopoiesis. The epigenome of terminally differentiating erythroid cells defines a distinct subset of highly specialized cells that are vastly dissimilar from other hematopoietic and nonhematopoietic cell types. These epigenomic and transcriptome data are powerful tools to study human erythropoiesis.

4.
Macromol Rapid Commun ; 40(17): e1800658, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30600572

RESUMO

A novel kind of water-soluble fluorescent hyperbranched poly(amino ester) (PAE) is prepared through a one-pot polycondensation reaction of citric acid (CA) and N-methyldiethanolamine (NMDEA). The PAE exhibits enhanced and red-shift fluorescence with increasing solution concentration, showing distinct aggregation-induced emission character. Interestingly, the resulting PAE exhibits tunable photoluminescence from blue, cyan, and green to red irradiated by altering the excitation wavelengths. Such unique emission of non-conjugated PAE is attributed to the clustering of ester and tertiary amine groups derived from PAE self-assembly aggregates. Moreover, the fluorescence of PAE is very sensitive to Fe3+ ions. The facile preparation and unique optical features make PAE potentially useful in numerous applications such as multicolor cellular imaging, Fe3+ ions probe, and light-emitting diodes.

5.
J Cell Mol Med ; 23(1): 194-204, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30394654

RESUMO

Diallyl disulfide (DADS), the main active component of the cancer fighting allyl sulfides found in garlic, has shown potential as a therapeutic agent in various cancers. Previous studies showed DADS induction of HL-60 cell differentiation involves down-regulation of calreticulin (CRT). Here, we investigated the mechanism of DADS-induced differentiation of human leukaemia cells and the potential involvement of CRT and CCAAT enhancer binding protein-α (C/EBPα). We explored the expression of CRT and C/EBPα in clinical samples (20 healthy people and 19 acute myeloid leukaemia patients) and found that CRT and C/EBPα expressions were inversely correlated. DADS induction of differentiation of HL-60 cells resulted in down-regulated CRT expression and elevated C/EBPα expression. In severe combined immunodeficiency mice injected with HL-60 cells, DADS inhibited the growth of tumour tissue and decreased CRT levels and increased C/EBPα in vivo. We also found that DADS-mediated down-regulation of CRT and up-regulation of C/EBPα involved enhancement of reactive oxidative species. RNA immunoprecipitation revealed that CRT bound C/EBPα mRNA, indicating its regulation of C/EBPα mRNA degradation by binding the UG-rich element in the 3' untranslated region of C/EBPα. In conclusion, the present study demonstrates the C/EBPα expression was correlated with CRT expression in vitro and in vivo and the molecular mechanism of DADS-induced leukaemic cell differentiation.

6.
Cell Physiol Biochem ; 47(6): 2613-2625, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29996119

RESUMO

BACKGROUND/AIMS: Alpha-synuclein (α-Syn) is a neuronal protein that is highly implicated in Parkinson's disease (PD), and protein phosphatase 2A (PP2A) is an important serine/threonine phosphatase that is associated with neurodegenerative diseases, such as PD. α-Syn can directly upregulate PP2A activity, but the underling mechanism remains unclear. Therefore, we investigated the molecular mechanism of α-Syn regulating PP2A activity. METHODS: α-Syn and its truncations were expressed in E.coli, and purified by affinity chromatography. PP2A Cα and its mutants were expressed in recombinant baculovirus, and purified by affinity chromatography combined with gel filtration chromatography. The interaction between α-Syn and PP2A Cα was detected by GST pull-down assay. PP2A activity was investigated by the colorimetric assay. RESULTS: The hydrophobic non-amyloid component (NAC) domain of α-Syn interacted with PP2A Cα and upregulated its activity. α-Syn aggregates reduced its ability to upregulate PP2A activity, since the hydrophobic domain of α-Syn was blocked during aggregation. Furthermore, in the hydrophobic center of PP2A Cα, the residue of I123 was responsible for PP2A to interact with α-Syn, and its hydrophilic mutation blocked its interaction with α-Syn as well as its activity upregulation by α-Syn. CONCLUSIONS: α-Syn bound to PP2A Cα by the hydrophobic interaction and upregulated its activity. Blocking the hydrophobic domain of α-Syn or hydrophilic mutation on the residue I123 in PP2A Cα all reduced PP2A activity upregulation by α-Syn. Overall, we explored the mechanism of α-Syn regulating PP2A activity, which might offer much insight into the basis underlying PD pathogenesis.


Assuntos
Mutação de Sentido Incorreto , Proteína Fosfatase 2C , Regulação para Cima , alfa-Sinucleína , Substituição de Aminoácidos , Linhagem Celular Tumoral , Humanos , Ligação Proteica , Domínios Proteicos , Proteína Fosfatase 2C/química , Proteína Fosfatase 2C/genética , Proteína Fosfatase 2C/metabolismo , alfa-Sinucleína/química , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
7.
Medicine (Baltimore) ; 97(21): e10681, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29794744

RESUMO

RATIONALE: This combination of fluticasone propionate (FP) and the long-acting ß2-agonist salmeterol (Salm) can control the symptoms of asthma and COPD better than FP or Salm on their own and better than the combination of inhaled corticosteroids plus montelukast. FP/Salm has been shown to control symptoms of asthma and COPD better than a double dose of inhaled steroids. The patient in our report had a history of COPD, and suffered relapse of RP when given only steroids. It is possible that COPD history helps explain this patient's more difficult treatment course. Therefore, this combination may be more effective than inhaled steroids for patients with a history of COPD. PATIENT CONCERS: This patient suffered adverse reactions triggered by methylprednisolone: weight gain, hyperglycaemia and sleep disturbance after more than two months of intravenous and oral prednisolone. These reactions disappeared when we switched the patients to FP/Salm maintenance therapy. DIAGNOSES: The patient underwent upper right lobectomy in September 2011. Immunohistochemistry indicated low squamous cell differentiation, and he was diagnosed with stage IIB disease (T2N1M0) according to the Union for International Cancer Control (UICC) (7th edition).One month after repeat radiotherapy, the patient experienced fever (37.6°C), cough, chest distress and shortness of breath. We performed serologic tests, laboratory tests for procalcitonin and C-reactive protein, as well as sputum and blood cultures to rule out bacterial infection. Chest CT showed consolidation with air bronchogram in the hilum of the right lung and ground-glass densities in the right lower lobe and left upper lobe. These radiographic signs are typical of RP. Since the patient required oxygen, he was diagnosed with grade III RP. INTERVENTIONS: After the patinet was diagnosed with grade III RP. The patient was immediately prescribed oxygen, anti-infectives for prophylaxis, treatments to facilitate expectoration and prevent asthma, and most importantly, intravenous methylprednisone at an initial dose of 60  per day. And we cut the steroid dose in half every one week when the patient's symptoms improved obviously, and the patchy shadow on the chest radiograph sharply reduced. Then we give him FP (500 mg)/Salm (50 mg) twice daily for two months. Then the dose was halved for an additional two months. OUTCOMES: The patient showed no signs of tumor or RP relapse by the last follow-up in March 2018. LESSONS: This maintenance therapy of FP/Salm for patient with grade III RP may help avoid relapse when steroid therapy is tapered, particularly for patients with a history of COPD. It may also reduce risk of steroid-associated adverse effects. Based on the results observed with our patient, we intend to design a prospective trial to assess the efficacy of FP/Salm when used as preventive treatment for patients at high risk of RP, and when used as maintenance treatment for patients with grade III RP.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Combinação Fluticasona-Salmeterol/uso terapêutico , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/tratamento farmacológico , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Pulmão/patologia , Pulmão/efeitos da radiação , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pneumonectomia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pneumonite por Radiação/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Chemistry ; 24(17): 4239-4244, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29411904

RESUMO

Chemosensors (CSs) with dynamically tunable detection ranges have important significance for their expansion in practical applications; however, most CSs possess an unchangeable detection limit. In this work, we report the first example of a supramolecular polymer vesicle (SPV) chemosensor with a dynamically tunable detection range. SPVs containing porphyrin (PP) moieties and ß-cyclodextrin (ß-CD)/azobenzene (Azo) host-guest interactions were first constructed. The obtained SPVs were used to detect Zn2+ with a high selectivity and sensitivity over a wide detection limit range of 8.67×10-9 to 1.99×10-11 under UV light irradiation. The corresponding sensing mechanism was attributed to the synergistic effects of the triple noncovalent interactions, including the metal-ligand coordination of PP/Zn2+ and the double host-guest interactions of ß-CD/Azo and ß-CD/PP.

9.
J Hematol Oncol ; 11(1): 19, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29433555

RESUMO

BACKGROUND: SF3B1 is a core component of splicing machinery. Mutations in SF3B1 are frequently found in myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ringed sideroblasts (RARS), characterized by isolated anemia. SF3B1 mutations have been implicated in the pathophysiology of RARS; however, the physiological function of SF3B1 in erythropoiesis remains unknown. METHODS: shRNA-mediated approach was used to knockdown SF3B1 in human CD34+ cells. The effects of SF3B1 knockdown on human erythroid cell differentiation, cell cycle, and apoptosis were assessed by flow cytometry. RNA-seq, qRT-PCR, and western blot analyses were used to define the mechanisms of phenotypes following knockdown of SF3B1. RESULTS: We document that SF3B1 knockdown in human CD34+ cells leads to increased apoptosis and cell cycle arrest of early-stage erythroid cells and generation of abnormally nucleated late-stage erythroblasts. RNA-seq analysis of SF3B1-knockdown erythroid progenitor CFU-E cells revealed altered splicing of an E3 ligase Makorin Ring Finger Protein 1 (MKRN1) and subsequent activation of p53 pathway. Importantly, ectopic expression of MKRN1 rescued SF3B1-knockdown-induced alterations. Decreased expression of genes involved in mitosis/cytokinesis pathway including polo-like kinase 1 (PLK1) was noted in SF3B1-knockdown polychromatic and orthochromatic erythroblasts comparing to control cells. Pharmacologic inhibition of PLK1 also led to generation of abnormally nucleated erythroblasts. CONCLUSIONS: These findings enabled us to identify novel roles for SF3B1 in human erythropoiesis and provided new insights into its role in regulating normal erythropoiesis. Furthermore, these findings have implications for improved understanding of ineffective erythropoiesis in MDS patients with SF3B1 mutations.


Assuntos
Eritropoese , Síndromes Mielodisplásicas/genética , Fosfoproteínas/genética , Fatores de Processamento de RNA/genética , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Linhagem Celular , Células Precursoras Eritroides/citologia , Células Precursoras Eritroides/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Humanos , Síndromes Mielodisplásicas/metabolismo
10.
Am J Hematol ; 93(4): 494-503, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29274096

RESUMO

Studies of human erythropoiesis have relied, for the most part, on the in vitro differentiation of hematopoietic stem and progenitor cells (HSPC) from different sources. Here, we report that despite the common core erythroid program that exists between cord blood (CB)- and peripheral blood (PB)-HSPC induced toward erythroid differentiation in vitro, significant functional differences exist. We undertook a comparative analysis of human erythropoiesis using these two different sources of HSPC. Upon in vitro erythroid differentiation, CB-derived cells proliferated 4-fold more than PB-derived cells. However, CB-derived cells exhibited a delayed kinetics of differentiation, resulting in an increased number of progenitors, notably colony-forming unit (CFU-E). The phenotypes of early erythroid differentiation stages also differed between the two sources with a significantly higher percentage of IL3R- GPA- CD34+ CD36+ cells generated from PB- than CB-HSPCs. This subset was found to generate both burst-forming unit (BFU-E) and CFU-E colonies in colony-forming assays. To further understand the differences between CB- and PB-HSPC, cells at eight stages of erythroid differentiation were sorted from each of the two sources and their transcriptional profiles were compared. We document differences at the CD34, BFU-E, poly- and orthochromatic stages. Genes exhibiting the most significant differences in expression between HSPC sources clustered into cell cycle- and autophagy-related pathways. Altogether, our studies provide a qualitative and quantitative comparative analysis of human erythropoiesis, highlighting the impact of the developmental origin of HSPCs on erythroid differentiation.


Assuntos
Envelhecimento/sangue , Células Precursoras Eritroides/citologia , Eritropoese/fisiologia , Adulto , Antígenos CD34/análise , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Células Precursoras Eritroides/efeitos dos fármacos , Eritropoese/genética , Eritropoetina/farmacologia , Sangue Fetal/citologia , Humanos , Recém-Nascido , Transcriptoma
11.
Mol Med Rep ; 17(1): 1035-1040, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115486

RESUMO

Malignant melanoma is the leading cause of mortality among the skin­associated diseases because of its highly metastatic nature and lethality. The aim of the present study was to evaluate antitumor and apoptosis effects of pomolic acid, a pentacyclic triterpene, against SK­MEL­2 human malignant melanoma cells. Its effect on cell migration and cell cycle arrest were also studied. An MTT assay was used to assess the cell cytotoxicity effects induced by pomolic acid. Fluorescence microscopy using acridine orange/propidium iodide and Hoechst 33342 staining, along with transmission electron microscopy (TEM), was used to study the effects of pomolic acid on apoptosis induction in these cells. The effects of pomolic acid on cell migration were studied using an in vitro wound healing assay. The effects of pomolic acid on cell cycle phase distribution were evaluated by flow cytometry using propidium iodide as fluorescent probe. The results revealed that pomolic acid induced significant dose­ and time­dependent antiproliferative effects in SK­MEL­2 human malignant melanoma cells, with IC50 values of 110.3, 88.1 and 79.3 µM after 24, 48 and 72 h, respectively. Pomolic acid­treated cells exhibited red fluorescence, and the intensity of this fluorescence increased in a dose­dependent manner, indicating apoptosis induction. After the cells were treated with 25, 75 and 150 µM pomolic acid, significant morphological alterations characteristic of apoptosis were observed by TEM, including loss of microvilli, a damaged plasma membrane, damaged cellular organelles and enlarged lysosomes. Pomolic acid also led to sub­G1 cell cycle arrest, and inhibited cancer cell migration in a dose­dependent manner. These results implicate pomolic acid as a potential therapeutic agent for the treatment of malignant melanoma.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Melanoma , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia
12.
Polymers (Basel) ; 10(11)2018 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-30961124

RESUMO

A novel graphene-based nanocomposite particles (NH2-rGO/WS2), composed of reduced graphene oxide (rGO) and tungsten disulfide (WS2) grafted with active amino groups (NH2-rGO/WS2), was successfully synthesized by an effective and facile method. NH2-rGO/WS2 nanoparticles were then used to fabricate new bismaleimide (BMI) composites (NH2-rGO/WS2/BMI) via a casting method. The results demonstrated that a suitable amount of NH2-rGO/WS2 nanoparticles significantly improved the mechanical properties of the BMI resin. When the loading of NH2-rGO/WS2 was only 0.6 wt %, the impact and flexural strength of the composites increased by 91.3% and 62.6%, respectively, compared to the neat BMI resin. Rare studies have reported such tremendous enhancements on the mechanical properties of the BMI resin with trace amounts of fillers. This is attributable to the unique layered structure of NH2-rGO/WS2 nanoparticles, fine interfacial adhesion, and uniform dispersion of NH2-rGO/WS2 in the BMI resin. Besides, the thermal gravimetrical analysis (TGA) revealed that the addition of NH2-rGO/WS2 could also improve the stability of the composites.

13.
Tumour Biol ; 39(4): 1010428317697554, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28378637

RESUMO

In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells. Tr1 cells were characterized by high interleukin 10 secretion and low Foxp3 expression and were enriched in the CD4+CD49b+LAG-3+ T-cell fraction. Macrophages derived from peripheral blood monocytes in the presence of modified melanoma-conditioned media demonstrated tumor-promoting capacity, exemplified by improving the proliferation of cocultured A375 malignant melanoma cells. But when primary Tr1 cells were present in the macrophage-A375 coculture, the growth of A375 cells was abrogated. The conventional CD25+ Treg cells, however, were unable to inhibit macrophage-mediated increase in tumor cell growth. Further analyses showed that Tr1 cells did not directly eliminate A375 cells, but mediated the killing of tumor-promoting macrophages through the secretion of granzyme B and perforin. The tumor-infiltrating interleukin 10+Foxp3-CD4+ T cells expressed very low levels of granzyme B and perforin, possibly suggested the downregulation of Tr1 cytotoxic capacity in melanoma tumors. Together, these data demonstrated an antitumor function of Tr1 cells through the elimination of tumor-promoting macrophages, which was not shared by conventional Tregs.


Assuntos
Granzimas/metabolismo , Macrófagos/fisiologia , Melanoma/imunologia , Perforina/metabolismo , Linfócitos T Reguladores/imunologia , Células Cultivadas , Citotoxicidade Imunológica , Humanos , Melanoma/metabolismo , Melanoma/patologia , Metástase Neoplásica , Células Tumorais Cultivadas
14.
Blood ; 129(14): 2002-2012, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-28167661

RESUMO

The ten-eleven translocation (TET) family of proteins plays important roles in a wide range of biological processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine. However, their function in erythropoiesis has remained unclear. We show here that TET2 and TET3 but not TET1 are expressed in human erythroid cells, and we explore the role of these proteins in erythropoiesis. Knockdown experiments revealed that TET2 and TET3 have different functions. Suppression of TET3 expression in human CD34+ cells markedly impaired terminal erythroid differentiation, as reflected by increased apoptosis, the generation of bi/multinucleated polychromatic/orthochromatic erythroblasts, and impaired enucleation, although without effect on erythroid progenitors. In marked contrast, TET2 knockdown led to hyper-proliferation and impaired differentiation of erythroid progenitors. Surprisingly, knockdown of neither TET2 nor TET3 affected global levels of 5mC. Thus, our findings have identified distinct roles for TET2 and TET3 in human erythropoiesis, and provide new insights into their role in regulating human erythroid differentiation at distinct stages of development. Moreover, because knockdown of TET2 recapitulates certain features of erythroid development defects characteristic of myelodysplastic syndromes (MDSs), and the TET2 gene mutation is one of the most common mutations in MDS, our findings may be relevant for improved understanding of dyserythropoiesis of MDS.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Dioxigenases/metabolismo , Eritropoese/fisiologia , Células-Tronco Hematopoéticas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Antígenos CD34/genética , Antígenos CD34/metabolismo , Proteínas de Ligação a DNA/genética , Dioxigenases/genética , Técnicas de Silenciamento de Genes , Células-Tronco Hematopoéticas/citologia , Humanos , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Proteínas Proto-Oncogênicas/genética
15.
Polymers (Basel) ; 9(9)2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30965748

RESUMO

Surface modification of graphene oxide (GO) is one of the most important issues to produce high performance GO/epoxy composites. In this paper, the imidazole ionic liquid (IMD-Si) was introduced onto the surface of GO sheets by a cheap and simple method, to prepare a reinforcing filler, as well as a catalyst in epoxy resin. The interlayer spacing of GO sheets was obviously increased by the intercalation of IMD-Si, which strongly facilitated the dispersibility of graphene oxide in organic solvents and epoxy matrix. The addition of 0.4 wt % imidazolium ionic liquid modified graphene oxide (IMD-Si@GO), yielded a 12% increase in flexural strength (141.3 MPa), a 26% increase in flexural modulus (4.69 GPa), and a 52% increase in impact strength (18.7 kJ/m²), compared to the neat epoxy. Additionally the IMD-Si@GO sheets could catalyze the curing reaction of epoxy resin-anhydride system significantly. Moreover, the improved thermal conductivities and thermal stabilities of epoxy composites filled with IMD-Si@GO were also demonstrated.

16.
Tumour Biol ; 2016 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-27709550

RESUMO

Metastatic melanoma is a rapidly progressing disease with high mortality rate and limited treatment options. Immunotherapy based on tumor-targeting cytotoxic T cell responses represents a promising strategy. To assist in its development, we examined the possibility and efficacy of using CD4+ cytotoxic T cells. The regulatory mechanisms controlling CD4+ T cell-mediated cytotoxicity were also investigated. We found that naturally occurring granzyme B and perforin-expressing CD4+ cytotoxic T cells can be recovered from metastatic melanoma patients at significantly elevated frequencies compared to those from healthy controls. These CD4+ cytotoxic T cells were also capable of killing autologous tumor cells harvested from metastatic melanoma, independent of CD8+ T cells or any other cell types. However, several restricting factors were observed. First, the cytolytic activity by CD4+ T cells required high MHC class II expression on melanoma cells, which was not satisfied in a subset of melanomas. Second, the granzyme B and perforin release by activated CD4+ cytotoxic T cells was reduced after coculturing with autologous melanoma cells, characterized by low LAMP-1 expression and low granzyme B and perforin secretion in the supernatant. This suggested that inhibitory mechanisms were present to suppress CD4+ cytotoxic T cells. Indeed, blockade of PD-1 and CTLA-4 had increased the cytolytic activity of CD4+ T cells but was only effective in MHC class II high but not MHC class II low melanomas. Together, our study showed that CD4+ T cell-mediated cytotoxicity could eliminate primary melanoma cells but the efficacy depended on MHC class II expression.

17.
Int J Clin Pharmacol Ther ; 54(5): 343-53, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26902505

RESUMO

Undecylenic acid can effectively control skin fungal infection, but the mechanism of its fungal inhibition is unclear. Hyphal growth of Candida albicans (C. albicans) and biofilm formation have been well recognized as important virulence factors for the initiation of skin infection and late development of disseminated infection. In this study, we seek to investigate antifungal mechanisms of undecylenic acid by evaluating the virulence factors of C. albicans during biofilm formation. We found that undecylenic acid inhibits biofilm formation of C. albicans effectively with optimal concentration above 3 mM. In the presence of this compound, the morphological transition from yeast to filamentous phase is abolished ultimately when the concentration of undecylenic acid is above 4 mM. Meanwhile, the cell surface is crumpled, and cells display an atrophic appearance under scanning electron microscopy even with low concentration of drug treatment. On the other hand, the drug treatment decreases the transcriptions of hydrolytic enzymes such as secreted aspartic protease, lipase, and phospholipase. Hyphal formation related genes, like HWP1, are significantly reduced in transcriptional level in drug-treated biofilm condition as well. The down-regulated profile of these genes leads to a poorly organized biofilm in undecylenic acid treated environment.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Ácidos Undecilênicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Candida albicans/patogenicidade , Relação Dose-Resposta a Droga , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Fatores de Virulência/metabolismo
18.
Polymers (Basel) ; 8(2)2016 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30979127

RESUMO

In this paper, we mainly described the reversible self-assembly of a backbone-thermoresponsive, long-chain, hyperbranched poly(N-isopropyl acrylamide) (LCHBPNIPAM) in aqueous solution. Here, we revealed a reversible self-assembly behavior of LCHBPNIPAM aqueous solution derived from temperature. By controlling the temperature of LCHBPNIPAM aqueous solution, we tune the morphology of the LCHBPNIPAM self-assemblies. When the solution temperature increased from the room temperature to the lower critical solution temperature of PNIPAM segments, LCHBPNIPAM self-assembled from multi-compartment vesicles into solid micelles. The morphology of LCHBPNIPAM self-assemblies changed from solid micelles to multi-compartment vesicles again when the temperature decreased back to the room temperature. The size presented, at first, an increase, and then a decrease, tendency in the heating-cooling process. The above thermally-triggered self-assembly behavior of LCHBPNIPAM aqueous solution was investigated by dynamic/static light scattering, transmission electron microscopy, atomic force microscopy, fluorescence spectroscopy, ¹H nuclear magnetic resonance in D2O, and attenuated total reflectance Fourier transform infrared spectroscopy. These results indicated that LCHBPNIPAM aqueous solution presents a reversible self-assembly process. The controlled release behaviors of doxorubicin from the vesicles and micelles formed by LCHBPNIPAM further proved the feasibility of these self-assemblies as the stimulus-responsive drug delivery system.

19.
Macromol Rapid Commun ; 37(2): 136-42, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26524219

RESUMO

In this Communication, novel water-soluble hyperbranched polysiloxanes (WHPSs) simultaneously containing hydroxyl and primary amine groups are developed. The polymers are constructed via melt polycondensation, that is, transesterification reaction between ethoxyl groups of (3-aminopropyl)triethoxysilane and hydroxyl groups of dihydric alcohols, using a one-step process under catalyst-free conditions. Surprisingly, the resultant WHPSs can emit bright blue fluorescence in the 100% solid state under the irradiation of UV light, and their photoluminescence intensities in aqueous solutions continuously go up along with increasing concentrations. Interestingly, their hydrolyzates display more intense luminescence compared to the unhydrolyzed. The efficient and easily controllable preparation strategy provides a remarkable and versatile platform for the fabrication of neoteric fluorescent materials for various potential applications.


Assuntos
Corantes Fluorescentes/química , Siloxanas/química , Água/química , Aminas/química , Catálise , Fluorescência , Corantes Fluorescentes/síntese química , Hidrólise , Radical Hidroxila/química , Siloxanas/síntese química , Soluções , Espectrometria de Fluorescência , Termodinâmica , Raios Ultravioleta
20.
Ecotoxicol Environ Saf ; 126: 14-22, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26707184

RESUMO

Incidental oral ingestion is the main exposure pathway by which human intake contaminants in both soil and indoor dust, and this is especially true for children as they frequently exhibit hand-to-mouth behaviour. Research on comprehensive health risk caused by incidental ingestion of both soil and indoor dust is limited. The aims of this study were to investigate the arsenic concentration and to characterize the health risks due to arsenic (As) exposure via soil and indoor dust in rural and urban areas of Hubei province within central China. Soil and indoor dust samples were collected from schools and residential locations and bioaccessibility of arsenic in these samples was determined by a simplified bioaccessibility extraction test (SBET). The total arsenic content in indoor dust samples was 1.78-2.60 times that measured in soil samples. The mean As bioaccessibility ranged from 75.4% to 83.2% in indoor dust samples and from 13.8% to 20.2% in soil samples. A Pearson's analysis showed that As bioaccessibility was significantly correlated with Fe and Al in soil and indoor dust, respectively, and activity patterns of children were utilised in the assessment of health risk via incidental ingestion of soil and indoor dust. The results suggest no non-carcinogenic health risks (HQ<1) or acceptable carcinogenic health risks (1×10(-6)

Assuntos
Poluição do Ar/análise , Arsênico/análise , Poeira/análise , Exposição Ambiental/análise , Poluentes do Solo/análise , Poluição do Ar/efeitos adversos , Arsênico/farmacocinética , Bioensaio/métodos , Disponibilidade Biológica , Criança , Pré-Escolar , China , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Atividades de Lazer , Masculino , Medição de Risco/métodos , População Rural/estatística & dados numéricos , Poluentes do Solo/farmacocinética , População Urbana/estatística & dados numéricos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA