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1.
Biomaterials ; 216: 119248, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226569

RESUMO

Neurodegenerative disorders such as Huntington's disease (HD) are fundamentally caused by accumulation of misfolded aggregate-prone proteins. Previous investigations have shown that these toxic protein aggregates could be degraded through autophagy induced by small molecules as well as by nanomaterials. However, whether engineered nanomaterials have the capacity to degrade these protein aggregates via the ubiquitin-proteasome system (UPS), the other major pathway for intracellular protein turnover, was unknown. Herein, we have synthesized biocompatible MnFe2O4 nanoparticles (NPs) and demonstrated their unique effect in accelerating the clearance of mutant huntingtin (Htt) protein exhibiting 74 glutamine repeats [Htt(Q74)]. UPS, rather than autophagy, was responsible for the efficient Htt(Q74) degradation facilitated by MnFe2O4 NPs. Meanwhile, we demonstrated that MnFe2O4 NPs enhanced K48-linked ubiquitination of GFP-Htt(Q74). Moreover, ubiqinlin-1, but not p62/SQSTM1, served as the ubiquitin receptor that mediated the enhanced degradation of Htt(Q74) by MnFe2O4 NPs. Our findings may have implications for developing novel nanomedicine for the therapy of HD and other polyglutamine expansion diseases.

2.
Nanoscale ; 11(24): 11789-11807, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31184642

RESUMO

Autophagy may represent a common cellular response to nanomaterials. In the present study, it was demonstrated that zinc oxide nanoparticle (ZON)-elicited autophagy contributes to tumor cell killing by accelerating the intracellular dissolution of ZONs and reactive oxygen species (ROS) generation. In particular, ZONs could promote Atg5-regulated autophagy flux without the impairment of autophagosome-lysosome fusion, which is responsible for ZON-elicited cell death in cancer cells. On the other hand, a further study revealed that a significant free zinc ion release in lysosomal acid compartments and sequential ROS generation in cells treated with ZONs were also associated with tumor cytotoxicity. Intriguingly, the colocalization between FITC-labeled ZONs and autophagic vacuoles indicates that the intracellular fate of ZONs is associated with autophagy. Moreover, the chemical or genetic inhibition of autophagy significantly reduced the level of intracellular zinc ion release and ROS generation separately, demonstrating that ZON-induced autophagy contributed toward cancer cell death by accelerating zinc ion release and sequentially increasing intracellular ROS generation. The modulation of autophagy holds great promise for improving the efficacy of tumor chemotherapy. Herein, ZONs were verified to enhance chemotherapy in both normal and drug-resistant cancer cells via synergistic autophagy elicitation. Further, this elicitation resulted in tremendous zinc ion release and ROS generation, which accounted for enhancing the tumor chemotherapy and overcoming drug resistance. No obvious changes in the expression level of P-gp proteins or the amount of doxorubicin uptake induced by ZONs in MCF-7/ADR cells also indicated that the increased zinc ion release and ROS generation via synergistic autophagy induction were responsible for overcoming the drug resistance. Finally, in vivo experiments involving animal models of 4T1 tumor cells revealed that the antitumor therapeutic effect of a combinatory administration obviously outperformed those of ZONs or free doxorubicin treatment alone at the same dose, which could be attenuated by the autophagy inhibitor wortmannin or ion-chelating agent EDTA. Taken together, our results reveal the mechanism wherein the autophagy induction by ZONs potentiates cancer cell death and a novel biological application for ZONs in adjunct chemotherapy in which autophagy reinforces zinc ion release and ROS generation.


Assuntos
Antineoplásicos , Doxorrubicina , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas , Neoplasias Experimentais/tratamento farmacológico , Óxido de Zinco , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Feminino , Células HeLa , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Espécies Reativas de Oxigênio/metabolismo , Óxido de Zinco/química , Óxido de Zinco/farmacologia
3.
Biomed Res Int ; 2019: 6543230, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30723742

RESUMO

Vasculogenic mimicry (VM) with the pattern of endothelial independent tubular structure formation lined by aggressive tumor cells mimics regular tumor blood vessels to ensure robust blood supply and correlates with the proliferation, invasion, metastasis, and poor prognosis of malignant tumors, which was demonstrated to be a major obstacle for resistance to antiangiogenesis therapy. Therefore, it is urgent to discover methods to abrogate the VM formation of tumors, which possesses important practical significance for improving tumor therapy. Brucine is a traditional medicinal herb extracted from seeds of Strychnos nux-vomica L. (Loganiaceae) exhibiting antitumor activity in a variety of cancer models. In the present study, the effect of brucine on vasculogenic mimicry and the related mechanism are to be investigated. We demonstrated that, in a triple-negative breast cancer cell line MDA-MB-231, brucine induced a dose-dependent inhibitory effect on cell proliferation along with apoptosis induction at higher concentrations. The further study showed that brucine inhibited cell migration and invasion with a dose-dependent manner. Our results for the first time indicated that brucine could disrupt F-actin cytoskeleton and microtubule structure, thereby impairing hallmarks of aggressive tumors, like migration, invasion, and holding a possibility of suppressing vasculogenic mimicry. Hence, the inhibitory effect of brucine on vasculogenic mimicry was further verified. The results illustrated that brucine significantly suppressed vasculogenic mimicry tube formation with a dose-dependent effect indicated by the change of the number of tubules, intersections, and mean length of tubules. The in-depth molecular mechanism of vasculogenic mimicry suppression induced by brucine was finally suggested. It was demonstrated that brucine inhibited vasculogenic mimicry which might be through the downregulation of erythropoietin-producing hepatocellular carcinoma-A2 and matrix metalloproteinase-2 and metalloproteinase-9.


Assuntos
Neovascularização Patológica/tratamento farmacológico , Estricnina/análogos & derivados , Strychnos nux-vomica/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Estricnina/química , Estricnina/farmacologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
4.
Biomater Sci ; 7(1): 272-286, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30467569

RESUMO

Treatment of infected bone defects still remains a formidable clinical challenge, and the design of bone implants with both anti-bacterial activity and -osteogenesis effects is nowadays regarded as a powerful strategy for infection control and bone healing. In the present study, bioresorbable porous-structured microspheres were fabricated from an amphiphilic block copolymer composed of poly(l-lactide) and poly(ethyl glycol) blocks. After being surface coated with mussel-inspired polydopamine, the microspheres were loaded with nanosilver via the reduction of silver nitrate and apatite via biomineralization in sequence. At optimized loading amounts, the nanosilver-loaded microspheres showed no unfavorable effects on the proliferation and differentiation of bone marrow mesenchymal stem cells despite preserving strong antibacterial activity in in vitro evaluations. For the critical-sized defects (φ = 8 mm) in the rat cranium that was pre-infected with Staphylococcus aureus, the filling of the dual-purpose microspheres demonstrated an effective way to kill bacteria in vivo, and in the meantime, it promoted new bone formation efficiently alongside the degradation of microspheres. Thus, the results suggested that bioresorbable microspheres with both osteoconductive and antibacterial activities were a good choice for treating infected bone defects.


Assuntos
Antibacterianos/uso terapêutico , Apatitas/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/uso terapêutico , Prata/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Apatitas/farmacologia , Linhagem Celular , Materiais Revestidos Biocompatíveis/farmacologia , Indóis/farmacologia , Indóis/uso terapêutico , Microesferas , Osteogênese/efeitos dos fármacos , Polímeros/farmacologia , Polímeros/uso terapêutico , Ratos , Ratos Sprague-Dawley , Prata/farmacologia , Crânio/efeitos dos fármacos , Crânio/lesões , Crânio/microbiologia
5.
Biomed Res Int ; 2018: 4780612, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29992145

RESUMO

Gynura formosana Kitam. belongs to the Compositae family and has been traditionally used for the prevention of cancer, diabetes, and inflammation in China. Previous studies had indicated that the ethyl acetate extract of Gynura formosana Kitam. leaves (EAEG) exhibited antioxidant and anti-inflammatory activity. In this report, we demonstrated that EAEG possessed potent anticancer activity through autophagy-mediated inhibition of cell proliferation. EAEG induced a strong cytostatic effect towards HeLa cells and, to a lesser extent, HepG2 and MCF-7 cells. This cytostatic effect of EAEG was not a consequence of increased apoptosis, as neither DNA fragmentation nor change in protein expression level for a number of apoptosis-related genes including Bid, Bax, Bcl-2, and caspase-3 was observed after EAEG treatment, and the apoptosis inhibitor Z-VAD-FMK did not inhibit the EAEG-elicited cytostatic effect. On the other hand, EAEG induced autophagy in a dose-dependent fashion, as shown by increased GFP puncta formation, enhanced conversion of the microtubule-associated protein light chain LC3-I to LC3-II, and downregulation of the p62 protein. Treating the HeLa cells with EAEG together with Chloroquine (CQ) further accelerated LC3 conversion and p62 clearance, indicating that EAEG induced complete autophagy flux. Importantly, the autophagy inhibitor 3-methyladenine (3MA) significantly abrogated the cytostatic effect of EAEG, strongly suggesting that EAEG inhibited HeLa cell proliferation through the induction of autophagy rather than apoptosis. Our results provided a novel and interesting mechanistic insight into the anticancer action of EAEG, supporting the traditional use of this plant for the treatment of the cancer.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Acetatos , Asteraceae , Autofagia , Linhagem Celular Tumoral , China , Feminino , Células HeLa , Humanos
6.
Small ; 13(7)2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27925395

RESUMO

The diverse biological effects of nanomaterials form the basis for their applications in biomedicine but also cause safety issues. Induction of autophagy is a cellular response after nanoparticles exposure. It may be beneficial in some circumstances, yet autophagy-mediated toxicity raises an alarming concern. Previously, it has been reported that upconversion nanoparticles (UCNs) elicit liver damage, with autophagy contributing most of this toxicity. However, the detailed mechanism is unclear. This study reveals persistent presence of enlarged autolysosomes in hepatocytes after exposure to UCNs and SiO2 nanoparticles both in vitro and in vivo. This phenomenon is due to anomaly in the autophagy termination process named autophagic lysosome reformation (ALR). Phosphatidylinositol 4-phosphate (PI(4)P) relocates onto autolysosome membrane, which is a key event of ALR. PI(4)P is then converted into phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 ) by phosphatidylinositol-4-phosphate 5-kinase. Clathrin is subsequently recruited by PI(4,5)P2 and leads to tubule budding of ALR. Yet it is observed that PI(4)P cannot be converted in nanoparticle-treated hepatocytes cells. Exogenous supplement of PI(4,5)P2 suppresses the enlarged autolysosomes in vitro. Abolishment of these enlarged autolysosomes by autophagy inhibitor relieves the hepatotoxicity of UCNs in vivo. The results provide evidence for disrupted ALR in nanoparticle-treated hepatocytes, suggesting that the termination of nanoparticle-induced autophagy is of equal importance as the initiation.


Assuntos
Autofagia , Hepatócitos/citologia , Hepatócitos/metabolismo , Lisossomos/metabolismo , Nanopartículas/química , Animais , Autofagia/efeitos dos fármacos , Células Cultivadas , Hepatócitos/efeitos dos fármacos , Fígado/metabolismo , Lisossomos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Nanopartículas/toxicidade , Fosfatos de Fosfatidilinositol/metabolismo
7.
Huan Jing Ke Xue ; 38(11): 4725-4732, 2017 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965418

RESUMO

The waste dump of an iron mine in Anhui Province has been abandoned for several decades. Pyrite in the exposed waste ores is oxidized by acidophiles and large amounts of metal ions and H2SO4 are released, resulting in the formation of an acid mine drainage (AMD) lake since 1970s. Besides the lake, there are also some small-scale AMD adjacent to the newly deposited waste ore. In order to study the acid generation potential of the waste ore and the related microbial communities, soil samples were taken from beside the AMD lake (1LL) and small-scale AMD (5J, 5Y, 6-1, 6-2, 6-3) and the physicochemical properties and microbial community of these samples were analyzed. The results reveal that all of samples were highly acidic and the pH of the 1LL sample was 2.77, while the other samples were even more acidic, at less than 2.6. The electrical conductivity (EC) (0.32 mS·cm-1) of the 1LL sample was obviously lower than the other samples (2.25-7.08 mS·cm-1), which indicates that the newly deposited waste ore contains higher ion concentrations. The Fe2+ concentration of the 1LL sample was only 0.80 mg·kg-1 but the other five samples were as high as 2.91-33.40 mg·kg-1. This suggests that most of the Fe2+ in the 1LL sample has been converted to Fe3+ after long-term oxidization. High-throughput sequencing results showed that most acidophiles in 1LL sample were Actinobacteria, Acidobacteria and Chloroflexi but the microbes in the remaining five samples were γ-Proteobacteria, Firmicutes and Nitrospira. The iron-sulfur oxidizing bacteria, such as Sulfobacillus, Leptospirillum, Acidithiobacillus, were scarce in the 1LL sample, while they highly abundant in the other five samples, which proves that the acid-generation process of the newly deposited waste ore is strong. However, the reduced iron and sulfur in the 1LL sample has nearly been depleted. Statistical analysis shows that the microbial composition of the 1LL sample is significantly different to that of the five newly deposited samples, illustrating that microbial community composition is remarkably influenced by physicochemical conditions.


Assuntos
Ácidos/metabolismo , Bactérias/classificação , Ferro , Mineração , Microbiologia do Solo , Bactérias/metabolismo , China , Concentração de Íons de Hidrogênio
8.
Small ; 12(41): 5759-5768, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27593892

RESUMO

Many nanomaterials are reported to disrupt lysosomal function and homeostasis, but how cells sense and then respond to nanomaterial-elicited lysosome stress is poorly understood. Nucleus translocation of transcription factor EB (TFEB) plays critical roles in lysosome biogenesis following lysosome stress induced by starvation. The authors previously reported massive cellular vacuolization, along with autophagy induction, in cells treated with rare earth oxide (REO) nanoparticles. Here, the authors identify these giant cellular vacuoles as abnormally enlarged and alkalinized endo/lysosomes whose formation is dependent on macropinocytosis. This vacuolization causes deactivation of mammalian target of rapamycin (mTOR), a TFEB-interacting kinase that resides on the lysosome membrane. Subsequently, TFEB is dephosphorylated at serine 142 and translocated into cell nucleus. This nucleus translocation of TFEB is observed only in vacuolated cells and it is critical for maintaining lysosome homeostasis after REO nanoparticle treatment, as knock-down of TFEB gene significantly compromises lysosome function and enhances cell death in nanoparticle-treated cells. Our results reveal that cellular vacuolization, which is commonly observed in cells treated with REOs and other nanomaterials, represents a condition of profound lysosome stress, and cells sense and respond to this stress by facilitating mTOR-dependent TFEB nucleus translocation in an effort to restore lysosome homeostasis.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Núcleo Celular/metabolismo , Lisossomos/metabolismo , Metais Terras Raras/química , Nanopartículas/química , Óxidos/química , Serina-Treonina Quinases TOR/metabolismo , Vacúolos/metabolismo , Álcalis/química , Sobrevivência Celular , Endossomos/metabolismo , Células HeLa , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Modelos Biológicos , Pinocitose , Transporte Proteico
9.
J Org Chem ; 81(1): 43-50, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26656574

RESUMO

A convenient approach for the synthesis of 1,4-diketones bearing an amino group has been developed through the K2CO3-catalyzed reaction of 2-oxindoles with enones with the assistance of atmospheric O2 via sequential Michael addition-oxidation-ring-cleavage process. The further intramolecular reaction leads to the formation of benzoazepinone, quinoline, and 3-oxindole derivatives.

10.
Biomaterials ; 73: 160-74, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26409001

RESUMO

Accelerating the clearance of intracellular protein aggregates through elevation of autophagy represents a viable approach for the treatment of neurodegenerative diseases. In our earlier report, we have demonstrated the enhanced degradation of mutant huntingtin protein aggregates through autophagy process induced by europium hydroxide nanorods [EHNs: Eu(III)(OH)3], but the underlying molecular mechanism of EHNs mediated autophagy was unclear. The present report reveals that EHNs induced autophagy does not follow the classical AKT-mTOR and AMPK signaling pathways. The inhibition of ERK1/2 phosphorylation using the specific MEK inhibitor U0126 partially abrogates the autophagy as well as the clearance of mutant huntingtin protein aggregates mediated by EHNs suggesting that nanorods stimulate the activation of MEK/ERK1/2 signaling pathway during autophagy process. In contrast, another mTOR-independent autophagy inducer trehalose has been found to induce autophagy without activating ERK1/2 signaling pathway. Interestingly, the combined treatment of EHNs and trehalose leads to more degradation of mutant huntingtin protein aggregates than that obtained with single treatment of either nanorods or trehalose. Our results demonstrate the rational that further enhanced clearance of intracellular protein aggregates, needed for diverse neurodegenerative diseases, may be achieved through the combined treatment of two or more autophagy inducers, which stimulate autophagy through different signaling pathways.


Assuntos
Európio/química , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hidróxidos/química , Nanotubos/química , Proteínas do Tecido Nervoso/química , Trealose/química , Adenina/análogos & derivados , Adenina/química , Androstadienos/química , Animais , Autofagia , Proteína 5 Relacionada à Autofagia , Butadienos/química , Linhagem Celular Tumoral , Sobrevivência Celular , Cloroquina/química , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Humanos , Proteína Huntingtina , Lisossomos/metabolismo , Macrolídeos/química , Camundongos , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/metabolismo , Doenças Neurodegenerativas/embriologia , Doenças Neurodegenerativas/metabolismo , Nitrilos/química , Fagossomos/química , Fosforilação , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Wortmanina
11.
BMC Nephrol ; 16: 10, 2015 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-25886601

RESUMO

BACKGROUND: Kimura's disease (KD) is a slowly progressing rare, benign inflammatory disorder of the soft tissues. It typically presents as subcutaneous tumor-like nodules, located most frequently in the head and neck region. KD is often accompanied by increased peripheral eosinophilia and elevated levels of serum immunoglobulin (Ig) E. There is renal involvement in approximately 12-16% of KD cases. We report the case of a 23-year-old Chinese man who was found to have KD associated with nephrotic syndrome. CASE PRESENTATION: A 23-year-old Chinese man presented with edema in both legs and a mass in ulnar side of his right upper arm on August 8(th) 2013. Before admission to our hospital, an ultrasound examination revealed swollen lymph nodes in the medial aspect of his right upper arm, proximal to the elbow. The patient was admitted on August 19(th) 2013 as a result of edema, severe proteinuria, and low serum albumin levels. He had a white blood cell count of 7.7 × 10(9) cells/L, 48.5% eosinophils, 4+ albuminuria, 24-hour urinary protein excretion 9.3 g, serum protein 50.3 g/L; serum albumin 16 g/L and IgE 1,510 IU/ml. A biopsy of the epitrochlear nodes revealed eosinophilic hyperplastic lymphogranulomatous tissue. A renal biopsy indicated focal segmental glomerulosclerosis (FSGS) (cellular variant) with no infiltration of eosinophil in renal interstitium. The results of immune-staining on the renal biopsy were negative for IgG, IgA, IgM, C3 and C1q. The electron microscopic analysis showed podocyte effacement. His final diagnosis was Kimura's disease associated with nephrotic syndrome. He received methylprednisolone therapy as well as symptomatic treatment, and was discharged with key indicators in normal range on September 17(th) 2013. During the year following, he had methylprednisolone at a maintenance dose of 8 mg/day, and no relapses occurred up to now. CONCLUSION: Methylprednisolone therapy is effective in KD associated with nephrotic syndrome, and long-term administration of methylprednisolone at maintenance dose may be a way to prevent relapses of KD.


Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Hiperplasia Angiolinfoide com Eosinofilia/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/complicações , Doenças Linfáticas/complicações , Metilprednisolona/uso terapêutico , Síndrome Nefrótica/complicações , Hiperplasia Angiolinfoide com Eosinofilia/complicações , Biópsia por Agulha , Seguimentos , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Humanos , Imuno-Histoquímica , Testes de Função Renal , Doenças Linfáticas/diagnóstico , Doenças Linfáticas/tratamento farmacológico , Imagem por Ressonância Magnética/métodos , Masculino , Monitorização Fisiológica , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
12.
Biomaterials ; 35(3): 899-907, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24169003

RESUMO

Autophagy is one of the well-known pathways to accelerate the clearance of protein aggregates, which contributes to the therapy of neurodegenerative diseases. Although there are numerous reports that demonstrate the induction of autophagy with small molecules including rapamycin, trehalose and lithium, however, there are few reports mentioning the clearance of aggregate-prone proteins through autophagy induction by nanoparticles. In the present article, we have demonstrated that europium hydroxide [Eu(III)(OH)3] nanorods can reduce huntingtin protein aggregation (EGFP-tagged huntingtin protein with 74 polyQ repeats), responsible for neurodegenerative diseases. Again, we have found that these nanorods induce authentic autophagy flux in different cell lines (Neuro 2a, PC12 and HeLa cells) through the expression of higher levels of characteristic autophagy marker protein LC3-II and degradation of selective autophagy substrate/cargo receptor p62/SQSTM1. Furthermore, depression of protein aggregation clearance through the autophagy blockade has also been observed by using specific inhibitors (wortmannin and chloroquine), indicating that autophagy is involved in the degradation of huntingtin protein aggregation. Since [Eu(III)(OH)3] nanorods can enhance the degradation of huntingtin protein aggregation via autophagy induction, we strongly believe that these nanorods would be useful for the development of therapeutic treatment strategies for various neurodegenerative diseases in near future using nanomedicine approach.


Assuntos
Autofagia/efeitos dos fármacos , Európio/farmacologia , Hidróxidos/farmacologia , Nanotubos/química , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Linhagem Celular , Európio/química , Humanos , Proteína Huntingtina , Hidróxidos/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutação , Nanotubos/ultraestrutura
13.
Eur J Med Chem ; 62: 405-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23385091

RESUMO

Peptide chaperon TD1 was discovered to facilitate several proteins' transdermal delivery via topical co-administration. To design a practical, safe system for advanced transdermal peptide, a novel method was carried out. Human epidermal growth factor (hEGF) was selected as the model biological agent and a fusion protein: TD1-hEGF was designed. Study showed that TD1-hEGF not only had the similar bioactivity with native hEGF, but also possessed considerable higher transdermal ability than hEGF and a co-administration of TD1 and hEGF. These results provided convincing evidence for the advantages of TD1-hEGF in cosmetic and medical applications. Moreover, the fusion pattern between the cargoes and TD1 offered a new approach to facilitate other hydrophilic drugs' transdermal delivery for therapeutic application.


Assuntos
Sistemas de Liberação de Medicamentos , Fator de Crescimento Epidérmico/química , Chaperonas Moleculares/química , Oligopeptídeos/química , Pele/metabolismo , Administração Cutânea , Animais , Células 3T3 BALB , Proliferação de Células , Células Cultivadas , Fator de Crescimento Epidérmico/administração & dosagem , Fator de Crescimento Epidérmico/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Chaperonas Moleculares/administração & dosagem , Chaperonas Moleculares/metabolismo , Oligopeptídeos/administração & dosagem , Oligopeptídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Absorção Cutânea
14.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 5): o1417, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22590303

RESUMO

In the title compound, C(14)H(11)Cl(2)NO, the two benzene rings are non-coplanar [dihedral angle = 60.9 (3)°]. In the crystal, an amide N-H⋯O hydrogen bond links the mol-ecules into chains which extend along (001).

15.
Virol Sin ; 25(1): 45-51, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20960283

RESUMO

The Crimean-congo hemorrhagic fever virus (CCHFV) is a geographically widespread fatal pathogen. Identification of the epitope regions of the virus is important for the diagnosis and epidemiological studies of CCHFV infections. In this study, expression vectors carrying series truncated fragments of the NP (nucleocapsid protein) gene from the S fragment of CCHFV strain YL04057 were constructed. The recombinant proteins were expressed in E.coli and purified for detection. The antigenic of the truncated fragments of NP was detected with a polyclonal serum (rabbit) and 2 monoclonal (mAbs) (14B7 and 43E5) against CCHFV by Western-blot analyses. The results showed that the three expressed constructs, which all contained the region 235AA to 305AA could be detected by mAbs polyclonal serum. The results suggest that region 235-305 aa of NP is a highly antigenic region and is highly conserved in the NP protein.


Assuntos
Mapeamento de Epitopos/métodos , Epitopos/imunologia , Vírus da Febre Hemorrágica da Crimeia-Congo/imunologia , Proteínas Mutantes/imunologia , Proteínas do Nucleocapsídeo/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Western Blotting , Epitopos/genética , Escherichia coli/genética , Expressão Gênica , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Proteínas Mutantes/genética , Proteínas do Nucleocapsídeo/genética , Coelhos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Deleção de Sequência
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