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1.
Intern Med J ; 50(9): 1115-1123, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31707755

RESUMO

BACKGROUND: H7N9 avian influenza is an infection of public health concern, in part because of its high mortality rate and pandemic potential. AIMS: To describe the clinical features of H7N9 avian influenza and the response to treatment. METHODS: Clinical, radiological and histopathological data, and treatment-related of H7N9-infected patients hospitalised during 2014-2017 were extracted and analysed. RESULTS: A total of 17 H7N9 patients (three females; mean age, 58.4 ± 13.7 years) was identified; of these six died. All patients presented with fever and productive cough; four patients had haemoptysis and 13 had chest distress and/or shortness of breath. Early subnormal white blood cell count and elevation of serum liver enzymes were common. Multilobar patchy shadows, rapid progression to ground-glass opacities, air bronchograms and consolidation were the most common imaging findings. Histopathological examination of lung tissue of three patients who died showed severe alveolar epithelial cell damage, with inflammatory exudation into the alveolar space and hyaline membrane formation; widened alveolar septae, prominent inflammatory cell infiltration; and hyperplasia of pneumocytes. Viral inclusions were found in the lung tissue of two patients. All patients received antiviral drugs (oseltamivir ± peramivir). Four patients carried the rs12252-C/C interferon-induced transmembrane protein-3 (IFITM3) genotype, while the others had the C/T genotype. CONCLUSIONS: H7N9 virus infection causes human influenza-like symptoms, but may rapidly progress to severe pneumonia and even death. Clinicians should be alert to the possibility of H7N9 infection in high-risk patients. The presence of the IFITM3 rs12252-C genotype may predict severe illness.


Assuntos
Subtipo H7N9 do Vírus da Influenza A , Influenza Humana , Pneumonia , Adulto , Idoso , China , Feminino , Humanos , Influenza Humana/tratamento farmacológico , Proteínas de Membrana , Pessoa de Meia-Idade , Pneumonia/virologia , Proteínas de Ligação a RNA , Estudos Retrospectivos
2.
Chin Med J (Engl) ; 132(22): 2705-2715, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31725455

RESUMO

BACKGROUND: Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. METHODS: The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. RESULTS: Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. CONCLUSION: Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fator de Transcrição Ikaros/metabolismo , MicroRNAs/metabolismo , Derrame Pleural Maligno/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Citometria de Fluxo , Humanos , Fator de Transcrição Ikaros/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Leucócitos Mononucleares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Derrame Pleural Maligno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Oncotarget ; 8(32): 52211-52224, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28881724

RESUMO

Gastric cancer (GC) is the third leading cause of cancer death due to its poor prognosis and limited treatment options. Evidence indicates that pseudogene-derived long noncoding RNAs (lncRNAs) may be important players in human cancer progression, including GC. In this paper, we report that a newly discovered pseudogene-derived lncRNA named DUXAP8, a 2107-bp RNA, was remarkably upregulated in GC. Additionally, a higher level of DUXAP8 expression in GC was significantly associated with greater tumor size, advanced clinical stage, and lymphatic metastasis. Patients with a higher level of DUXAP8 expression had a relatively poor prognosis. Further experiments revealed that knockdown of DUXAP8 significantly inhibited cell proliferation and migration, as documented in the SGC7901 and BGC823 cell lines. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that DUXAP8 could epigenetically suppress the expression of PLEKHO1 by binding to EZH2 and SUZ12 (two key components of PRC2), thus promoting GC development. Taken together, our findings suggest that the pseudogene-derived lncRNA DUXAP8 promotes the progression of GC and is a potential therapeutic target for GC intervention.

4.
PLoS One ; 11(2): e0148848, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26894626

RESUMO

PURPOSE: Intranasal administration of phospholipid-based gelatin nanoparticles (GNP) was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP) on hemiparkinsonian rats. METHODS: The SP-loaded gelatin nanoparticles (SP-GNP) were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM). The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA) induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH), phosphorylated c-Jun protein (p-c-Jun) and Caspase-3 (Cas-3) expressed in substantia nigra (SN) region of hemiparkinsonian rats. RESULTS: PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration. CONCLUSIONS: With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis.


Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Gelatina/química , Nanopartículas/química , Neurotransmissores/administração & dosagem , Substância P/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Biomarcadores , Caspase 3/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Masculino , Nanopartículas/ultraestrutura , Neurotransmissores/química , Oxidopamina/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Ratos , Substância P/química , Tirosina 3-Mono-Oxigenase/metabolismo
5.
Drug Des Devel Ther ; 9: 1955-62, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25897205

RESUMO

BACKGROUND: The aim of this study was to investigate the protective role of intranasally administered substance P-loaded gelatin nanoparticles (SP-GNPs) against 6-hydroxydopamine (6-OHDA)-induced apoptosis in vitro and in vivo, and to provide a new strategy for treating brain pathology, such as Parkinson's disease. METHODS: SP-GNPs were prepared by a water-in-water emulsion method, and their stability, encapsulating efficiency, and loading capacity were evaluated. PC-12 cells were used to examine the enhancement of growth and inhibition of apoptosis by SP-GNPs in vitro using MTT assays. In the in vivo study, hemiparkinsonian rats were created by intracerebroventricular injection of 6-OHDA. The rats then received intranasal SP-GNPs daily for 2 weeks. Functional improvement was assessed by quantifying rotational behavior, and the degree of apoptosis was assessed by immunohistochemical staining for caspase-3 in the substantia nigra region. RESULTS: PC-12 cells with 6-OHDA-induced disease treated with SP-GNPs showed higher cell viability than their untreated counterparts, and cell viability increased as the concentration of substance P (SP) increased, indicating that SP could enhance cell growth and inhibit the cell apoptosis induced by 6-OHDA. Rats with 6-OHDA-induced hemiparkinsonism treated with SP-GNPs made fewer rotations and showed less staining for caspase-3 than their counterparts not treated with SP, indicating that SP protects rats with 6-OHDA-induced hemiparkinsonism from apoptosis and therefore demonstrates their functional improvement. CONCLUSION: Intranasal delivery of SP-GNPs protects against 6-OHDA-induced apoptosis both in vitro and in vivo.


Assuntos
Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Gelatina/química , Nanopartículas/química , Oxidopamina/antagonistas & inibidores , Substância P/administração & dosagem , Substância P/farmacologia , Administração Intranasal , Animais , Caspase 3/análise , Caspase 3/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Masculino , Estrutura Molecular , Oxidopamina/administração & dosagem , Oxidopamina/farmacologia , Células PC12 , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Substância P/química , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia
6.
J Control Release ; 186: 22-31, 2014 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-24815422

RESUMO

Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality among the diabetic patients and currently there is no effective means to reverse its pathological progress. Basic fibroblast growth factor (bFGF) has shown promise as a molecular therapy for DCM, but its delivery is inefficient and non-specific. In the present study, a therapy combining nanoparticle (NP) carrier and ultrasound-targeted microbubble destruction (UTMD) was reported the first time for bFGF delivery to the heart of diabetic rats. bFGF-loaded NP (bFGF-NP) were prepared with Poloxamer 188-grafted heparin copolymer using water-in-water technique, and the morphology, encapsulation efficiency, and bioactivity of bFGF-NP were studied. The cellular uptake and cytotoxicity of bFGF-NP were evaluated with primary cultures of the left ventricular (LV) cardiomyocytes in vitro. Therapeutic effects of bFGF-NP/UTMD on the heart of DCM rats were studied by measuring LV systolic and diastolic functions, hemodynamic characteristics and indicators of cardiac remodeling including myocardial collagen volume fraction and capillary density. Results demonstrated that bFGF-NP showed good round morphology, efficient bFGF encapsulation and stable bioactivity of bFGF in vitro. bFGF-NP/UTMD combined treatment significantly enhanced the efficiency of bFGF cellular uptake (P<0.05) without obvious cytotoxicity. Significant improvements (P<0.05) in both cardiac functions and tissue morphology in the DCM rats were observed in bFGF-NP/UTMD group. These were not achievable using free bFGF, bFGF-NP or UTMD treatment alone. Our results show that combining a non-viral vector with UTMD technique is an effective strategy to deliver bFGF to the heart, and the resulting growth factor therapy has demonstrated potential to reverse the progress of DCM by restoring the cardiac functions and even the structure of damaged cardiac tissues.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Microbolhas , Nanopartículas/administração & dosagem , Animais , Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/fisiopatologia , Fator 2 de Crescimento de Fibroblastos/química , Coração/efeitos dos fármacos , Coração/fisiopatologia , Heparina/química , Miocárdio/metabolismo , Miocárdio/patologia , Nanopartículas/química , Poloxâmero/química , Ratos Sprague-Dawley , Ultrassom , Função Ventricular Esquerda/efeitos dos fármacos
7.
Nanomedicine ; 10(4): 755-64, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24200526

RESUMO

Lipid nanoparticles with solid matrix have been given increasing attention due to their biodegradable status and ability to entrap a variety of biologically active compounds. In this study, new phospholipid-based gelatin nanoparticles encapsulating basic fibroblast growth factor (bFGF) were developed to target the brain via nasal administration. Treatment effects were assessed by quantifying rotational behavior, monoamine neurotransmitter levels and tyrosine hydroxylase expression in 6-hydroxydopamine induced hemiparkinsonian rats. The gelatin nanostructured lipid carriers (GNLs) were prepared by a water-in-water emulsion method and then freeze-dried. The GNLs possessed better profile than gelatin nanoparticles (GNs), with particle size 143±1.14nm and Zeta potential -38.2±1.2mV. The intranasal GNLs efficiently enriched exogenous bFGF in olfactory bulb and striatum without adverse impact on the integrity of nasal mucosa and showed obvious therapeutic effects on hemiparkinsonian rats. Thus, GNLs are attractive carriers for nose-to-brain drug delivery, especially for unstable macromolecular drugs such as bFGF. FROM THE CLINICAL EDITOR: This team of authors reports the development of phospholipid-based gelatin nanoparticles encapsulating basic fibroblast growth factor to target the brain via intranasal administration. A rat model of hemiparkinsonism was applied demonstrating a good safety profile and an obvious therapeutic effect.


Assuntos
Portadores de Fármacos/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Gelatina/farmacologia , Lipídeos/farmacologia , Nanopartículas , Doença de Parkinson Secundária/tratamento farmacológico , Administração Intranasal , Animais , Corpo Estriado/fisiopatologia , Portadores de Fármacos/química , Fator 2 de Crescimento de Fibroblastos/química , Gelatina/química , Lipídeos/química , Bulbo Olfatório/fisiopatologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/fisiopatologia , Ratos
8.
PLoS One ; 8(8): e73178, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24015296

RESUMO

Despite progress in the design of advanced surgical techniques, stenosis recurs in a large percentage of vascular anastomosis. In this study, a novel heparin-poloxamer (HP) hydrogel was designed and its effects for improving the quality and safety of vascular anastomosis were studied. HP copolymer was synthesized and its structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ((1)H-NMR). Hydrogels containing HP were prepared and their important characteristics related to the application in vascular anastomosis including gelation temperature, rheological behaviour and micromorphology were measured. Vascular anastomosis were performed on the right common carotid arteries of rabbits, and the in vivo efficiency and safety of HP hydrogel to achieve vascular anastomosis was verified and compared with Poloxamer 407 hydrogel and the conventional hand-sewn method using Doppler ultrasound, CT angiograms, scanning electron microscopy (SEM) and histological technique. Our results showed that HP copolymer displayed special gel-sol-gel phase transition behavior with increasing temperature from 5 to 60 °C. HP hydrogel prepared from 18 wt% HP solution had a porous sponge-like structure, with gelation temperature at approximately 38 °C and maximum elastic modulus at 10,000 Pa. In animal studies, imaging and histological examination of rabbit common jugular artery confirmed that HP hydrogel group had similar equivalent patency, flow and burst strength as Poloxamer 407 group. Moreover, HP hydrogel was superior to poloxamer 407 hydrogel and hand-sewn method for restoring the functions and epithelial structure of the broken vessel junctions after operation. By combining the advantages of heparin and poloxamer 407, HP hydrogel holds high promise for improving vascular anastomosis quality and safety.


Assuntos
Artéria Carótida Primitiva/cirurgia , Heparina/química , Hidrogéis/química , Poloxâmero/química , Segurança , Anastomose Cirúrgica/instrumentação , Anastomose Cirúrgica/métodos , Animais , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/ultraestrutura , Angiografia Cerebral , Humanos , Controle de Qualidade , Coelhos
9.
J Microencapsul ; 30(6): 538-45, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23489016

RESUMO

Biotin was conjugated on poloxamer to prepare biotin-poloxamer (BP) conjugate micelles for chemotherapeutics. Epirubicin (EPI) was encapsulated in BP micelles. The EPI-loaded BP micelles were characterized in terms of size, ζ-potential, morphology, drug loading, drug encapsulation and drug release. Marrow leukemic HL-60 cells were used for evaluating the in vitro cytotoxicity of EPI-loaded BP micelles. Nude mice were axillainoculated subcutaneously HL-60 cells to establish tumour model for investigating the inhibition effects of EPI-loaded BP micelles. From the results, the sizes of these nanoparticles were about 100 nm. Fluorescence microscope observation supported the enhanced cellular uptake of the micelles. The order of the inhibition on tumour volume growth was: EPI-loaded BP micelles >EPI-loaded MATP micelles >EPI-loaded poloxamer micelles >EPI. BP micelles showed significant antitumour activity and low toxicity, compared with the non-targeted micelles. With the advantage of EPR effect and tumour-targeting potential, BP conjugate micelles might be developed as a new system for chemotherapeutics.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Biotina/química , Epirubicina/administração & dosagem , Micelas , Neoplasias/tratamento farmacológico , Poloxâmero/química , Animais , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Epirubicina/farmacocinética , Epirubicina/uso terapêutico , Células HL-60 , Humanos , Masculino , Camundongos , Camundongos Nus , Neoplasias/patologia
10.
Cancer Lett ; 330(1): 74-83, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23186833

RESUMO

Multidrug resistance (MDR) is one of the major reasons for the failure of cancer chemotherapy. A newly reported liposome carrier, propylene glycol liposomes (EPI-PG-liposomes) were made to load epirubicin (EPI) which enhanced EPI absorption in MDR tumor cells to overcome the drug resistance. MDA-MB 435 and their mutant resistant (MDA-MB 435/ADR) cells were used to examine the cellular uptake and P-gp function in vitro for EPI-PG-liposomes by fluorescence microscopy and FCM, respectively. Mammary tumor model was also established to investigate the tumor growth inhibition and pharmacodynamics of EPI-PG-liposomes in vivo. Morphology evaluation showed that EPI-PG-liposomes had a homogeneous spherical shape with an average diameter of 182 nm. Based on cell viability assay, fluorescent microscopy examination, and EPI uptake assay, EPI-PG-liposomes exhibited an effective growth inhibition not only in MDA-MB-435 cells, but also in MDA-MB 435/ADR cells. EPI-PG-liposomes have high permeability not only on tumor cell membrane, but also on cell nucleus membrane. P-gp function assay showed that the anticancer action of EPI-PG-liposomes was not related to P-gp efflux pump, suggesting that PG-liposomes would not affect the normal physiological functions of membrane proteins. EPI-PG-liposomes also showed a better antitumor efficacy compared to EPI solution alone. With high entrapment efficiency, spherical morphology and effective inhibition on MDR cancer cells, EPI-PG-liposomes may represent a better chemotherapeutic vectors for cancer targeted therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Epirubicina/administração & dosagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Epirubicina/química , Epirubicina/farmacocinética , Epirubicina/farmacologia , Feminino , Humanos , Lipossomos/administração & dosagem , Lipossomos/química , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Propilenoglicol/administração & dosagem , Propilenoglicol/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
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