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1.
Vaccines (Basel) ; 12(2)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38400198

RESUMO

Zika virus (ZIKV) is an emerging flavivirus that causes congenital syndromes including microcephaly and fetal demise in pregnant women. No commercial vaccines against ZIKV are currently available. We previously generated a chimeric ZIKV (ChinZIKV) based on the Chaoyang virus (CYV) by replacing the prME protein of CYV with that of a contemporary ZIKV strain GZ01. Herein, we evaluated this vaccine candidate in a mouse model and showed that ChinZIKV was totally safe in both adult and suckling immunodeficient mice. No viral RNA was detected in the serum of mice inoculated with ChinZIKV. All of the mice inoculated with ChinZIKV survived, while mice inoculated with ZIKV succumbed to infection in 8 days. A single dose of ChinZIKV partially protected mice against lethal ZIKV challenge. In contrast, all the control PBS-immunized mice succumbed to infection after ZIKV challenge. Our results warrant further development of ChinZIKV as a vaccine candidate in clinical trials.

2.
Vaccines (Basel) ; 11(7)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37515065

RESUMO

The genus Flavivirus is a group of arthropod-borne single-stranded RNA viruses, which includes important human and animal pathogens such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), Dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Tick-borne encephalitis virus (TBEV). Reverse genetics has been a useful tool for understanding biological properties and the pathogenesis of flaviviruses. However, the conventional construction of full-length infectious clones for flavivirus is time-consuming and difficult due to the toxicity of the flavivirus genome to E. coli. Herein, we applied a simple, rapid, and bacterium-free circular polymerase extension reaction (CPER) method to synthesize recombinant flaviviruses in vertebrate cells as well as insect cells. We started with the de novo synthesis of the JEV vaccine strain SA-14-14-2 in Vero cells using CPER, and then modified the CPER method to recover insect-specific flaviviruses (ISFs) in mosquito C6/36 cells. Chimeric Zika virus (ChinZIKV) based on the Chaoyang virus (CYV) backbone and the Culex flavivirus reporter virus expressing green fluorescent protein (CxFV-GFP) were subsequently rescued in C6/36 cells. CPER is a simple method for the rapid generation of flaviviruses and other potential RNA viruses. A CPER-based recovery system for flaviviruses of different host ranges was established, which would facilitate the development of countermeasures against flavivirus outbreaks in the future.

3.
Adv Sci (Weinh) ; 10(24): e2301759, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37350493

RESUMO

Developing a multifunctional nanoplatform to achieve efficient theranostics of tumors through multi-pronged strategies remains to be challenging. Here, the design of the intelligent redox-responsive generation 3 (G3) poly(amidoamine) dendrimer nanogels (NGs) loaded with gold nanoparticles (Au NPs) and chemotherapeutic drug toyocamycin (Au/Toy@G3 NGs) for ultrasound-enhanced cancer theranostics is showcased. The constructed hybrid NGs with a size of 193 nm possess good colloidal stability under physiological conditions, and can be dissociated to release Au NPs and Toy in the reductive glutathione-rich tumor microenvironment (TME). The released Toy can promote the apoptosis of cancer cells through endoplasmic reticulum stress amplification and cause immunogenic cell death to maturate dendritic cells. The loaded Au NPs can induce the conversion of tumor-associated macrophages from M2-type to antitumor M1-type to remodulate the immunosuppressive TME. Combined with antibody-mediated immune checkpoint blockade, effective chemoimmunotherapy of a pancreatic tumor mouse model can be realized, and the chemoimmunotherapy effect can be further ultrasound enhanced due to the sonoporation-improved tumor permeability of NGs. The developed Au/Toy@G3 NGs also enable Au-mediated computed tomography imaging of tumors. The constructed responsive dendrimeric NGs tackle tumors through a multi-pronged chemoimmunotherapy strategy targeting both cancer cells and immune cells, which hold a promising potential for clinical translations.


Assuntos
Dendrímeros , Nanopartículas Metálicas , Neoplasias Pancreáticas , Animais , Camundongos , Nanogéis , Ouro , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Oxirredução , Macrófagos , Microambiente Tumoral , Neoplasias Pancreáticas
4.
Br J Radiol ; 96(1145): 20221086, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36883677

RESUMO

OBJECTIVES: Bladder cancer is among the most prevalent urothelial malignancies. Radiomics-based preoperative prediction of Ki67 and histological grade will facilitate clinical decision-making. METHODS: This retrospective study recruited 283 bladder cancer patients between 2012 and 2021. Multiparameter MRI sequences included: T1WI, T2WI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging. The radiomics features of intratumoral and peritumoral regions were extracted simultaneously. Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) algorithms were employed to select the features. Six machine learning-based classifiers were adopted to construct the radiomics models, and the best was chosen for the model construction. RESULTS: The mRMR and LASSO algorithms were more suitable for Ki67 and histological grade, respectively. Additionally, Ki67 had a higher proportion of intratumoral features, while peritumoral features accounted for a greater proportion of the histological grade. Random forests performed the best in predicting both pathological outcomes. Consequently, the multiparameter MRI (MP-MRI) models achieved area under the curve (AUC) values of 0.977 and 0.852 for Ki67 in training and test sets, respectively, and 0.972 and 0.710 for the histological grade. CONCLUSION: Radiomics holds the potential to predict multiple pathological outcomes of bladder cancer preoperatively and are expected to provide clinical decision-making guidance. Furthermore, our work inspired the process of radiomics research. ADVANCES IN KNOWLEDGE: This study demonstrated that different feature selection techniques, segmentation regions, classifiers, and MRI sequences will affect the performance of the model. We systematically demonstrated that radiomics can predict histological grade and Ki67.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Antígeno Ki-67/metabolismo , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgia
5.
J Magn Reson Imaging ; 58(2): 379-391, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36426965

RESUMO

BACKGROUND: Radiomics-based preoperative evaluation of lymph node metastasis (LNM) and histological grade (HG) might facilitate the decision-making for pancreatic cancer and further efforts are needed to develop effective models. PURPOSE: To develop multiparametric MRI (MP-MRI)-based radiomics models to evaluate LNM and HG. STUDY TYPE: Retrospective. POPULATION: The pancreatic cancer patients from the main center (n = 126) were assigned to the training and validation sets at a 4:1 ratio. The patients from the other center (n = 40) served as external test sets. FIELD STRENGTH/SEQUENCE: A 3.0 T and 1.5 T/T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement T1-weighted imaging. ASSESSMENT: A total of 10,686 peritumoral and intratumoral radiomics features were extracted which contained first-order, shape-based, and texture features. The following three-step method was applied to reduce the feature dimensionality: SelectKBest (a function from scikit-learn package), least absolute shrinkage and selection operator (LASSO), and recursive feature elimination based on random forest (RFE-RF). Six classifiers (random forest, logistic regression, support vector machine, K-nearest neighbor, decision tree, and XGBOOST) were trained and selected based on their performance to construct the clinical, radiomics, and combination models. STATISTICAL TESTS: Delong's test was used to compare the models' performance. P value less than 0.05 was considered significant. RESULTS: Twelve significant features for LNM and 11 features for HG were obtained. Random forest and logistic regression performed better than the other classifiers in evaluating LNM and HG, respectively, according to the surgical pathological results. The best performance was obtained with the models that combined peritumoral and intratumoral features with area under curve (AUC) values of 0.944 and 0.892 in the validation and external test sets for HG and 0.924 and 0.875 for LNM. DATA CONCLUSION: Radiomics holds the potential to evaluate LNM and HG of pancreatic cancer. The combination of peritumoral and intratumoral features will make models more accurate. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.


Assuntos
Metástase Linfática , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias Pancreáticas , Humanos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Imageamento por Ressonância Magnética , Metástase Linfática/patologia , Estudos Retrospectivos
6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-980153

RESUMO

Objective @# To survey the current situation and analyze the relevant influencing factors of sleep quality in adolescent patients with temporomandibular joint anterior disc displacement. @*Methods@#This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. A convenience sampling method was used to investigate 120 adolescent patients with temporomandibular joint anterior disc displacement in the outpatient department of stomatology in a grade A tertiary hospital in Shanghai using the general data questionnaire, the Pittsburgh sleep quality index scale (PSQI), the Chinese middle school student mental health scale (MMHI-60) and the pain visual analog scale (VAS). Descriptive analysis, single factor analysis, correlation analysis and multiple regression analysis were used to explore the relevant influencing factors. @* Results@#The PSQI score of adolescent patients with temporomandibular joint anterior disc displacement in this study was 7.77 ± 4.63. There was a statistically significant difference in sleep quality among patients with different academic pressures and levels of sleep bruxism (P<0.05). The sleep quality score was positively correlated with the pain score (r = 0.45, P<0.001) and positively correlated with the psychological score (r = 0.74, P<0.001). The degree of pain can affect the patient's sleep quality, and those with good mental health have better sleep quality. The results of regression analysis showed that academic stress (OR = 2.511, 95% CI =1.307 ~ 4.828), bruxism (OR = 3.694, 95% CI = 1.394 ~ 9.791), pain score (OR = 2.104, 95% CI =1.095 ~ 4.041) and psychological score (OR = 1.039, 95% CI = 1.021 ~ 1.058) were statistically significant.@*Conclusion @#The sleep quality of adolescent patients with temporomandibular joint anterior disc displacement is generally poor. Academic pressure, sleep bruxism, pain and mental health are the influencing factors of sleep quality.

7.
Int Immunopharmacol ; 113(Pt A): 109308, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36274487

RESUMO

BACKGROUND: A large-scale outbreak of Zika virus (ZIKV) has occurred in Brazil and other South American countries, and has rapidly spread to 60 countries and regions worldwide since 2015, but no approved anti-ZIKV vaccines are available as of 2021. METHODS: We developed four types of anti-ZIKV DNA vaccine candidates: VPC-NS1, VPC-prME, VPC-prME-NS1, and VPC-EIII-NS1. They were developed against the structural proteins prM and E, and non-structural protein 1 (NS1) of ZIKV using the mammalian cell expression vector pcDNA3.1(+) as the backbone. For immunization, we intramuscularly injected mice with each vaccine candidate (n = 12 to 15 per group) on day 0 and day 14, with mice injected with phosphate-buffered saline (PBS) and pcDNA3.1(+) backbone vector as controls. On day 7, 21, and 35 after initial immunization, the effect of DNA vaccines was evaluated by ZIKV-specific humoral immunity determined by enzyme-linked immunosorbent assay (ELISA), ZIKV-specific T cell immunity determined by intracellular cytokine staining by flow cytometry and serum neutralization capacity determined by plaque reduction neutralization test (PRNT50) assay. RESULTS: The sequencing results showed that DNA vaccine vectors were successfully constructed. Western blotting and immunofluorescence results demonstrated the successful expression of immunogens carried by the DNA vaccines. On day 21 and 35 after the initial immunization, the levels of serum total immunoglobulin (Ig)G in all vaccine-given groups were slightly higher (approximately 1.5- to 2-fold) than those in the control groups. By contrast, ZIKV-specific IgG levels of all vaccine-given groups were significantly higher (approximately 10- to 1000- fold) than those of the control groups. The PRNT50 assay showed that the average serum dilution factors for neutralizing half ZIKV virions from vaccine-given groups were at least 32-fold (highest, 93-fold), while the sera from control group showed no protection. For cellular immunity, the proportions of CD11b+ myeloid cells, CD19+ B lymphocytes and CD3+ T lymphocytes in the mouse spleens as well as the percentages of CD4+ and CD8+ subsets of T cell were not changed 35 days after initial immunization. By contrast, the proportions of ZIKV-specific CD4+T cell and CD8+T cell in all vaccine-given groups were 2- to 10-folds and 2- to 30-fold than those in the control groups, respectively. CONCLUSION: All four DNA vaccines designed for the ZIKV induced neutralizing IgGs and cellular immune responses against ZIKV. Particularly, VPC-EIII-NS1 induced high level of humoral response comparable to the vaccine candidate containing prM, E and NS1 polyprotein, suggesting a potent reduced ADE effect and reserved neutralizing activity. Our findings may provide guidance for improving safety of anti-ZIKV vaccines in the future.


Assuntos
Vacinas de DNA , Vacinas Virais , Infecção por Zika virus , Zika virus , Camundongos , Animais , Zika virus/genética , Zika virus/química , Anticorpos Antivirais , Infecção por Zika virus/prevenção & controle , Brasil , Anticorpos Neutralizantes , Mamíferos
8.
Altern Ther Health Med ; 28(6): 124-131, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35751898

RESUMO

Objective: This study aimed to investigate the effect of the Bushen-Shugan (BSSG) method on pregnancy outcomes, serum D-dimer (D-D), platelet aggregation rate, homocysteine (Hcy) and antithrombin III (AT-III) in patients with recurrent miscarriage complicated by anxiety and depression. Methods: From December 2016 to December 2019, 100 patients with recurrent miscarriage combined with anxiety and depression were enrolled in our study, and a prospective randomized trial was carried out. Patients were randomly assigned to either the control group or the BSSG group via the random number table method. Traditional Chinese medicine (TCM) syndrome scores, laboratory indicators and psychological changes were compared in the 2 groups before and after treatment. Results: After treatment, the primary, secondary and total TCM syndrome scores in the 2 groups were lower, and the scores in the BSSG group were significantly lower than in the control group. The clinical curative effect in the BSSG group was significantly higher (92% vs 76%) than in the control group. The levels of ß-HCG, P, E2 and AT-III in the 2 groups were higher, while levels of D-D, platelet aggregation rate and Hcy were lower than before treatment. The Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores were lower after treatment in both groups, and the scores in the BSSG group were significantly lower than in the control group. Conclusions: The BSSG method may be worthy of consideration because it improves pregnancy outcomes in patients with recurrent miscarriage complicated by anxiety and depression.


Assuntos
Aborto Habitual , Depressão , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Depressão/complicações , Depressão/tratamento farmacológico , Feminino , Humanos , Gravidez , Resultado da Gravidez , Estudos Prospectivos
9.
Front Oncol ; 12: 839621, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198452

RESUMO

OBJECTIVES: This study aims to develop and evaluate multiparametric MRI (MP-MRI)-based radiomic models as a noninvasive diagnostic method to predict several biological characteristics of prostate cancer. METHODS: A total of 252 patients were retrospectively included who underwent radical prostatectomy and MP-MRI examinations. The prediction characteristics of this study were as follows: Ki67, S100, extracapsular extension (ECE), perineural invasion (PNI), and surgical margin (SM). Patients were divided into training cohorts and validation cohorts in the ratio of 4:1 for each group. After lesion segmentation manually, radiomic features were extracted from MP-MRI images and some clinical factors were also included. Max relevance min redundancy (mRMR) and recursive feature elimination (RFE) based on random forest (RF) were adopted to select features. Six classifiers were included (SVM, KNN, RF, decision tree, logistic regression, XGBOOST) to find the best diagnostic performance among them. The diagnostic efficiency of the construction models was evaluated by ROC curves and quantified by AUC. RESULTS: RF performed best among the six classifiers for the four groups according to AUC values (Ki67 = 0.87, S100 = 0.80, ECE = 0.85, PNI = 0.82). The performance of SVM was relatively the best for SM (AUC = 0.77). The number and importance of DCE features ranked first in the models of each group. The combined models of MP-MRI and clinical characteristics showed no significant difference compared with MP-MRI models according to Delong's tests. CONCLUSIONS: Radiomics models based on MP-MRI have the potential to predict biological characteristics and are expected to be a noninvasive method to evaluate the risk stratification of prostate cancer.

10.
ACS Nano ; 15(12): 20377-20390, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34860014

RESUMO

Development of innovative nanomedicine formulations to traverse the blood-brain barrier (BBB) for effective theranostics of glioma remains a great challenge. Herein, we report the creation of macrophage membrane-camouflaged multifunctional polymer nanogels coloaded with manganese dioxide (MnO2) and cisplatin for magnetic resonance (MR) imaging-guided chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Redox-responsive poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) formed via precipitation polymerization were in situ loaded with MnO2 and physically encapsulated with cisplatin to have a mean size of 106.3 nm and coated with macrophage membranes to have a good colloidal stability. The generated hybrid NGs display dual pH- and redox-responsive cisplatin and Mn(II) release profiles and can deplete glutathione (GSH) rich in tumor microenvironment through reaction with disulfide-containing cross-linkers within the NGs and MnO2. The thus created Mn(II) enables enhanced CDT through a Fenton-like reaction and T1-weighted MR imaging, while the loaded cisplatin not only exerts its chemotherapy effect but also promotes the reactive oxygen species generation to enhance the CDT efficacy. Importantly, the macrophage membrane coating rendered the hybrid NGs with prolonged blood circulation time and ability to traverse BBB for specific targeted chemotherapy/CDT of orthotopic glioma. Our study demonstrates a promising self-adaptive and cooperative NG-based nanomedicine platform for highly efficient theranostics of glioma, which may be extended to tackle other difficult cancer types.


Assuntos
Glioma , Nanopartículas , Linhagem Celular Tumoral , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Humanos , Macrófagos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Compostos de Manganês , Nanogéis , Óxidos , Polímeros , Nanomedicina Teranóstica , Microambiente Tumoral
11.
Colloids Surf B Biointerfaces ; 185: 110625, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31734089

RESUMO

Multifunctional nanocarriers, which can be used for molecular imaging and drug delivery simultaneously, favor the fabrication of theranostic platforms in a less cost- and time-consuming way. Polyethylene glycol (PEG)-modified manganese dioxide (MnO2) nanosheets (PEG-MnO2), used as two-dimensional nanomaterials, not only possess the high surface-to-volume ratio necessary for drug delivery but also display a redoxable property in the tumor microenvironment, producing Mn2+ ions for magnetic resonance imaging (MRI). In this study, we constructed a PEG-MnO2-OPN siRNA nanocomplex via a modular streptavidin bridge for the theranostic treatment of renal carcinoma in vitro and in vivo. This strategy of utilizing PEG-MnO2 nanosheets for OPN siRNA delivery showed effective tumor growth inhibition of 786-O tumor-bearing mice, and such a process could be monitored by the activated T1-weight MRI, illustrating the promising potential of PEG-MnO2 nanosheets for the fabrication of an MRI-based theranostic system.


Assuntos
Técnicas de Transferência de Genes , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/terapia , Imageamento por Ressonância Magnética , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Inativação Gênica , Humanos , Neoplasias Renais/diagnóstico , Compostos de Manganês/química , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Osteopontina/genética , Óxidos/química , Polietilenoglicóis/química
12.
Int J Nanomedicine ; 14: 9513-9524, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819447

RESUMO

BACKGROUND: Early diagnosis of renal cell carcinoma is extremely significant for the effective treatment of kidney cancer. The development of AS1411 aptamer modified Mn-MoS2 QDs provides a promising fluorescence/magnetic resonance (MR) dual-modal imaging probe for the precise diagnosis of renal clear cell carcinoma. METHODS: In this work, Mn-MoS2 QDs were synthesized through a simple "bottom-up" one-step hydrothermal method. AS1411 aptamer was modified on the Mn-MoS2 QDs to improve the specificity to renal cell carcinoma. The characteristics of Mn-MoS2 QDs were confirmed by transmission electronic microscopy (TEM), atomic force microscope (AFM), X-ray photoelectron spectrometer (XPS), photoluminescence (PL) emission spectra, etc. Cellular fluorescence labelling was investigated using the Mn-MoS2 QDs and AS1411-Mn-MoS2 QDs. The T1-weighted MR imaging was assessed by the in vitro MR cell imaging and in vivo MR imaging. Finally, the long-term toxicity of Mn-MoS2 QDs was investigated by the hematology and histological analysis. RESULTS: The prepared Mn-MoS2 QDs exhibited excellent aqueous property, intense fluorescence, low toxicity, high quantum yield of 41.45% and high T1 relaxivity of 16.95 mM-1s-1. After conjugated with AS1411 aptamer, the AS1411-Mn-MoS2 QDs could specifically fluorescently label the renal carcinoma cells and present a specific MRI signal enhancement in the tumor region of mice bearing renal carcinoma tumors. Furthermore, Mn-MoS2 QDs revealed low toxicity to the mice via hematology and histological analysis. CONCLUSION: These results demonstrated the potential of AS1411-Mn-MoS2 QD as a novel nanoprobe for targeted MR imaging and fluorescence labelling of renal cell carcinoma.


Assuntos
Aptâmeros de Nucleotídeos/química , Carcinoma de Células Renais/diagnóstico por imagem , Dissulfetos/química , Imageamento por Ressonância Magnética , Manganês/química , Molibdênio/química , Oligodesoxirribonucleotídeos/química , Pontos Quânticos/química , Coloração e Rotulagem , Animais , Morte Celular , Linhagem Celular Tumoral , Dissulfetos/toxicidade , Feminino , Fluorescência , Humanos , Neoplasias Renais/diagnóstico por imagem , Manganês/toxicidade , Camundongos , Molibdênio/toxicidade , Pontos Quânticos/toxicidade , Pontos Quânticos/ultraestrutura
13.
RSC Adv ; 9(60): 34837-34846, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-35530716

RESUMO

With the advantages and development of MRI nano-contrast agents (CAs), increasing number of MRI-based theranostic nanoparticles have emerged. Liposome, as a biosafe nanocarrier has been used phase III trial for cancer treatment. In this study, liposome was employed as a nanocarrier to co-encapsulate MRI nano-contrast agent poly(ethylene glycol)-grafted manganese oxide (PEG-MnO) and anticancer drug paclitaxel (PTX) for the fabrication of a novel theranostic nanocomplex. After being further modified with AS1411 aptamer, the obtained nanoprobe AS1411-liposome-PEG-MnO-PTX displayed the potential of simultaneous MRI diagnosis and therapy of renal carcinoma in vitro and in vivo. It was found that compared with PEG-MnO nano-CA, liposome-PEG-MnO and AS1411-liposome-PEG-MnO presented a stronger MR contrast enhancement effect in the tumor and longer retention time in the tumor region. More importantly, the introduction of AS1411 aptamer further enhanced the MRI effect and the tumor growth inhibition effect, showing its potential use as a theranostic nanoprobe for renal carcinoma.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(6): 705-711, 2017 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28606241

RESUMO

OBJECTIVE: To observe the effects of recombinant fusion protein interleukin (IL)-18 on the expression of immune-inflammatory factors in the mice infected with Staphylococcus aureus (SA), and to investigate the mechanism of action of IL-18 in defense of SA infection in vivo. METHODS: A total of 40 specific pathogen-free female BLAB/c mice were randomly divided into four groups: control, SA infection, immunized, and intervention. A mouse model of SA infection was established by nasal inoculation with SA liquid. The immunized group and the intervention group were intranasally given IL-18 before SA modeling, and then the SA infection group and the intervention group received the nasal inoculation with SA liquid; the control group was treated with phosphate buffered saline instead. The levels of IL-4, interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), IgM in the serum and bronchoalveolar lavage fluid (BALF) of mice were measured by enzyme-linked immunosorbent assay. The expression of macrophage inflammatory protein (MIP)-1α mRNA and MIP-2ß mRNA in the lung tissue of mice were determined by real-time fluorescent quantitative PCR. RESULTS: Compared with the control group, the SA infection group and the immunized group had significantly higher levels of IL-4, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA and MIP-2ß mRNA in the lung tissue (P<0.05); the SA infection group had a significantly lower level of IFN-γ and a significantly higher level of TNF in the serum and BALF (P<0.05); the immunized group had a significantly higher level of IFN-γ in the serum and BALF (P<0.05). Compared with the SA infection group, the intervention group had significantly higher levels of IL-4, IFN-γ, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA in the lung tissue. In contrast, the intervention group showed a significantly lower level of TNF in the serum and BALF and expression of MIP-2ß mRNA in the lung tissue (P<0.05). All the above indicators in the intervention group were significantly higher than those in the control group (P<0.05), except the serum level of IFN-γ. CONCLUSIONS: In the mice infected with SA, the recombinant fusion protein IL-18 by mucosal immunity can affect inflammatory factors in the serum and BALF and the expression of MIP-1α mRNA and MIP-2ß mRNA in the lung tissue to promote the anti-infective immune response and enhance the ability to clear pathogens.


Assuntos
Interleucina-18/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Quimiocina CCL3/análise , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Interferon gama/sangue , Interleucina-4/sangue , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes de Fusão/farmacologia , Infecções Estafilocócicas/imunologia
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 15(3): 175-8, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23498756

RESUMO

OBJECTIVE: To investigate changes in serum complement, immunoglobulins and lymphocyte subsets in children with common and severe bronchial pneumonia, and the role of immune function testing in bronchial pneumonia. METHODS: Twenty children with common bronchial pneumonia, 20 with severe bronchial pneumonia and 20 healthy children (as controls) were enrolled in this study. Immunization rate scattering turbidimetry and six-color flow cytometry were used to detect changes in serum levels of IgA, IgG and IgM, complement C3 and C4 and CD3(+), CD4(+), CD8(+), CD16(+), CD56(+) and CD19(+) cells. RESULTS: The IgA levels of children with common and severe pneumonia were significantly lower than in the control group (P<0.05). The IgG level of children with severe pneumonia was significantly lower than in the control group (P<0.05). There were no significant differences in the levels of IgM and complement C3 and C4 between the two pneumonia groups and the control group (P>0.05). Compared with the controls, the children with severe pneumonia showed significantly lower CD4(+) and CD3(+) counts (P<0.05) and a significantly higher CD19(+) count (P<0.05), and the CD16(+) and CD56(+) counts of children with severe pneumonia were significantly lower than in the controls and in children with common pneumonia (P<0.05). There were no differences in CD8(+) count and CD4(+)/CD8(+) ratio between the two pneumonia groups and the control group (P>0.05). CONCLUSIONS: Immune dysfunction exists in children with bronchial pneumonia, especially those with severe pneumonia. Changes in immune function are correlated with the severity of pneumonia. Immune function testing in children with pneumonia has important clinical significance.


Assuntos
Broncopneumonia/imunologia , Pré-Escolar , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Lactente , Células Matadoras Naturais/imunologia , Masculino , Subpopulações de Linfócitos T/imunologia
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 11(11): 909-12, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-20113659

RESUMO

OBJECTIVE: Cysteinyl leukotriene (CysLTs) plays an important role in airway inflammation and remodeling in asthma. Measurement of urinary leukotriene E(4) (LTE(4)) is a sensitive and noninvasive method of assaying total body CysLTs level. This study aimed to evaluate the clinical significance of urinary leukotriene E(4) (LTE(4)) in childhood asthma. METHODS: Sixty children with acute asthma were randomly divided into montelukast (leukotriene receptor antagonist) treatment and conventional treatment groups (n = 30 each). Urinary LTE(4) levels were measured using ELISA and the airway resistance Rint was assessed by the lung function instrument at the acute and the convalescence phases. Twenty healthy children were used as the control group. RESULTS: Urinary LTE(4) levels in asthmatic children at the acute and the convalescence phases were significantly higher than those in the control group (p<0.01). The urinary LTE(4) levels at the convalescence phase were significantly reduced compared with those at the acute phase in asthmatic children (p<0.01). More significantly decreased urinary LTE(4) levels were noted in the montelukast treatment group than the conventional treatment group at the convalescence phase (p<0.01). In the acute phase, there was no correlation between urinary LTE4 level and Rint in asthmatic children. CONCLUSIONS: Urinary LTE(4) level is significantly increased in children with acute asthma. Urinary LTE(4) is a useful marker for the diagnosis of asthma and can be as a predictor of asthma control and marker of susceptibility to treatment with leukotriene receptor antagonists.


Assuntos
Asma/urina , Leucotrieno E4/urina , Resistência das Vias Respiratórias , Asma/diagnóstico , Asma/fisiopatologia , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino
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