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1.
RSC Adv ; 13(31): 21296-21299, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37456544

RESUMO

Compounds PTZ-MBZ (methyl 3-(10H-phenothiazin-10-yl)benzoate) and DMAC-MBZ (methyl 3-(9,9-dimethylacridin-10(9H)-yl)benzoate) were conveniently synthesized, and they exhibited TADF properties with lifetimes of 0.80 and 2.17 µs, respectively. The spatially separated highest occupied molecular orbital and lowest unoccupied molecular orbital resulted in a very small singlet-triplet energy gap of 0.0152 eV and 0.0640 eV, respectively. Thermally activated delayed fluorescence materials with short lifetime could be used as promising luminescent materials for organic light-emitting diodes.

2.
Front Immunol ; 14: 1149119, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969205

RESUMO

Mucous membrane pemphigoid (MMP) is a type of subepithelial autoimmune bullous disease, affecting various mucosae, occasionally with skin lesions. Both diagnosis and treatment of MMP are difficult. Although multiple autoantigens have been identified for MMP, the pathogenesis of MMP is still unclear. In this study, we presented a female MMP case with extensive oral mucosal lesions and skin lesions, particularly on the extremities. IgG and IgA autoantibodies against multiple autoantigens including BP180, laminin 332, integrinα6ß4 and desmoglein 3, and IgM autoantibodies against BP180 were identified during the disease course. Compared with IgG autoantibodies, the levels of IgA autoantibodies against various autoantigens decreased more significantly with improvement of clinical features after the initiation of treatments. Our findings indicated the importance of comprehensive autoantibody screening for different immunoglobulin types and autoantigens at multiple time points for the precise diagnosis of various autoimmune bullous diseases, and the significant involvement of IgA autoantibodies into the pathogenesis of MMP.


Assuntos
Doenças Autoimunes , Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Humanos , Feminino , Penfigoide Mucomembranoso Benigno/diagnóstico , Autoanticorpos , Imunoglobulina A , Colágenos não Fibrilares , Autoantígenos , Mucosa , Imunoglobulina G
5.
Strahlenther Onkol ; 198(8): 744-751, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35486127

RESUMO

PURPOSE: The purpose of this study is to investigate the effect of plan complexity on the dosimetry, delivery accuracy, and interplay effect in lung stereotactic body radiation therapy (SBRT) using volumetric modulated arc therapy (VMAT) with 6 MV flattening-filter-free (FFF) beam. METHODS: Twenty patients with early stage non-small cell lung cancer were included. For each patient, high-complexity (HC) and low-complexity (LC) three-partial-arc VMAT plans were optimized by adjusting the normal tissue objectives and the maximum monitoring units (MUs) for a Varian TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, CA, USA) using 6 MV FFF beam. The effect of plan complexity was comprehensively evaluated in three aspects: (1) The dosimetric parameters, including CI, D2cm, R50, and dose-volume parameters of organs at risk were compared. (2) The delivery accuracy was assessed by pretreatment quality assurance for two groups of plans. (3) The motion-induced dose deviation was evaluated based on point dose measurements near the tumor center by using a programmable phantom. The standard deviation (SD) and maximum dose difference of five measurements were used to quantify the interplay effect. RESULTS: The dosimetry of HC and LC plans were similar except the CI (1.003 ± 0.032 and 1.026 ± 0.043, p = 0.030) and Dmax to the spinal cord (10.6 ± 3.2 and 9.9 ± 3.0, p = 0.012). The gamma passing rates were significantly higher in LC plans for all arcs (p < 0.001). The SDs of HC and LC plans ranged from 0.5-16.6% and 0.03-2.9%, respectively, under the conditions of one-field, two-field, and three-field delivery for each plan with 0.5, 1, 2, and 3 cm motion amplitudes. The maximum dose differences of HC and LC plans were 34.5% and 9.1%, respectively. CONCLUSION: For lung VMAT SBRT, LC plans have a higher delivery accuracy and a lower motion-induced dose deviation with similar dosimetry compared with HC plans.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Radioterapia de Intensidade Modulada , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Pulmão/efeitos da radiação , Neoplasias Pulmonares/patologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
6.
Nano Res ; 15(5): 4334-4343, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35126877

RESUMO

Ca2+ plays critical roles in the development of diseases, whereas existing various Ca regulation methods have been greatly restricted in their clinical applications due to their high toxicity and inefficiency. To solve this issue, with the help of Ca overexpressed tumor drug resistance model, the phytic acid (PA)-modified CeO2 nano-inhibitors have been rationally designed as an unprecedentedly safe and efficient Ca2+ inhibitor to successfully reverse tumor drug resistance through Ca2+ negative regulation strategy. Using doxorubicin (Dox) as a model chemotherapeutic drug, the Ca2+ nano-inhibitors efficiently deprived intracellular excessive free Ca2+, suppressed P-glycoprotein (P-gp) expression and significantly enhanced intracellular drug accumulation in Dox-resistant tumor cells. This Ca2+ negative regulation strategy improved the intratumoral Dox concentration by a factor of 12.4 and nearly eradicated tumors without obvious adverse effects. Besides, nanocerias as pH-regulated nanozyme greatly alleviated the adverse effects of chemotherapeutic drug on normal cells/organs and substantially improved survivals of mice. We anticipate that this safe and effective Ca2+ negative regulation strategy has potentials to conquer the pitfalls of traditional Ca inhibitors, improve therapeutic efficacy of common chemotherapeutic drugs and serves as a facile and effective treatment platform of other Ca2+ associated diseases. Electronic Supplementary Material: Supplementary material (further details of the XRD pattern of CeO2, TEM images, XPS spectra, cellular uptake study, cytotoxicity data, apoptosis study, biodistribution, and biosecurity of nanocerias in vivo, etc.) is available in the online version of this article at 10.1007/s12274-022-4069-0.

7.
Front Immunol ; 12: 825226, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35095927

RESUMO

Autoimmune bullous diseases (AIBDs), presenting cutaneous and/or mucosal bullous lesions, are classified into pemphigus and pemphigoid diseases. A longtime observation for complicated AIBD cases is rarely reported. In this study, serum samples of one AIBD patient were collected at seven different time points during the disease course including a relapse, which were examined by our conventional and newly developed methods for the detection of autoantibodies. Interestingly, we found changes of both the presence and the titers of various autoantibodies in accordance with the changes of clinical features during the whole disease course, which indicated that the patient started as bullous pemphigoid and relapsed as concurrence of bullous pemphigoid and mucosal-dominant-type pemphigus vulgaris.


Assuntos
Autoantígenos/imunologia , Autoimunidade , Penfigoide Bolhoso/imunologia , Substituição de Aminoácidos , Autoanticorpos/imunologia , Autoantígenos/química , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Penfigoide Bolhoso/diagnóstico , Peptídeos/química , Peptídeos/imunologia
8.
Int J Biol Macromol ; 120(Pt A): 1225-1231, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30170052

RESUMO

A novel nano fluorescent starch, starch-bearing 3-epoxypropoxy fluorescein (ST-EF) was developed by a simple method. First, 3-epoxypropoxy fluorescein (EF) was prepared via a nucleophilic substitution reaction between fluorescein and epichlorohydrin. Then, ST-EF was synthesized via a ring-opening reaction to attach fluorescein to native cassava starch chains. The degree of substitution (DS) of ST-EF was determined by ultraviolet-visible spectrophotometry. The 1H nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, fourier transformed infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), dynamic laser scattering (DLS), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to characterize ST-EF. Fluorescent properties of ST-EF in water were studied. The results showed that the nano fluorescent starch shows strong fluorescence as fluorescein, and can be used as a fluorescent polymer in various applications, especially in biomedicine.


Assuntos
Fluoresceína/síntese química , Nanopartículas/química , Polímeros/síntese química , Amido/síntese química , Varredura Diferencial de Calorimetria , Epicloroidrina/química , Fluoresceína/química , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier , Amido/química , Água/química , Difração de Raios X
9.
J Nat Prod ; 79(12): 3127-3133, 2016 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-27958735

RESUMO

Picrasidine C (1), a dimeric ß-carboline-type alkaloid isolated from the root of Picrasma quassioides, was identified to have PPARα agonistic activity by a mammalian one-hybrid assay from a compound library. Among the PPAR subtypes, 1 selectively activated PPARα in a concentration-dependent manner. Remarkably, 1 also promoted PPARα transcriptional activity by a peroxisome proliferator response element-driven luciferase reporter assay. Furthermore, 1 induced the expression of PPARα-regulated genes involved in lipid, glucose, and cholesterol metabolism, such as CPT-1, PPARα, PDK4, and ABCA1, which was abrogated by the PPARα antagonist MK-886, indicating that the effect of 1 was dependent on PPARα activation. This is the first report to demonstrate 1 to be a subtype-selective PPARα agonist with potential application in treating metabolic diseases, such as hyperlipidemia, atherosclerosis, and hypercholesterolemia.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Carbolinas/isolamento & purificação , Carbolinas/farmacologia , PPAR alfa/agonistas , Picrasma/química , Alcaloides/química , Animais , Aterosclerose/tratamento farmacológico , Carbolinas/química , Colesterol/metabolismo , Glucose/metabolismo , Hipercolesterolemia/tratamento farmacológico , Indóis/farmacologia , Metabolismo dos Lipídeos , Lipídeos , Camundongos , Estrutura Molecular , PPAR alfa/genética , Fatores de Transcrição/metabolismo
10.
J Nat Prod ; 79(4): 879-85, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27025413

RESUMO

Recently, growing evidence of the pivotal roles of peroxisome proliferator-activated receptor (PPAR) ß/δ in various physiological functions, including lipid homeostasis, cancer, and inflammation, has raised interest in this receptor. In this study, the naturally occurring dimeric alkaloid picrasidine N (1) from Picrasma quassioides was identified as a novel PPARß/δ agonist from a library consisting of plant extracts and natural compounds using a mammalian one-hybrid assay, and this compound was characterized. Compound 1 activated PPARß/δ but did not activate or slightly activated PPARα and PPARγ. Furthermore, a peroxisome proliferator response element-driven luciferase reporter gene assay demonstrated that 1 enhanced PPARß/δ transcriptional activity. Moreover, 1 selectively induced mRNA expression of ANGPTL4, which is a PPAR target gene. This observation is quite different from previously identified synthetic PPARß/δ agonists, which can induce the expression of not only ANGPTL4 but also other PPAR target genes, such as ADRP, PDK4, and CPT-1. These results demonstrate that 1 is a potent subtype-selective and gene-selective PPARß/δ agonist, suggesting its potential as a lead compound for further drug development. This compound would also be a useful chemical tool for elucidating the mechanism of PPARß/δ-regulated specific gene expression and the biological significance of PPARß/δ.


Assuntos
Alcaloides/farmacologia , Picrasma/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Regulação da Expressão Gênica , Estrutura Molecular , PPAR alfa/agonistas , PPAR delta/agonistas , PPAR gama/agonistas , PPAR beta/agonistas
11.
Oncol Lett ; 5(5): 1439-1447, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23760551

RESUMO

Traditional Chinese medicine (TCM) has been demonstrated to have potent cytotoxic activity against certain malignant tumors. Ionizing radiation (IR) is one of the most effective methods used in the clinical treatment of cancer. The drawback of a single formula is that it limits the treatment efficacy for cancer, while comprehensive strategies require additional theoretical support. However, a combination of different antitumor treatment modalities is advantageous in restricting the non-specific toxicity often observed with an extremely high dose of a single regimen. The induction of apoptotic cell death is a significant process in tumor cells following radiotherapy or chemotherapy, and resistance to these treatments has been linked to a low propensity for apoptosis. Autophagy is a response of cancer cells to IR or chemotherapy, and involves the prominent formation of autophagic vacuoles in the cytoplasm. In this review, the synergistic effects of TCM and radiotherapy are summarized and the underlying mechanisms are illustrated, providing new therapeutic strategies for cancer.

12.
Saudi Med J ; 32(3): 254-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21384060

RESUMO

OBJECTIVE: To design the expression of fusion proteins containing one or 2 thrombopoietin mimetic peptide (TMP). METHODS: This study was conducted at Harbin Pharmaceutical Group Research and Development Center, Harbin, China from June 2009 to January 2010. We designed the protein that was fused to the C-terminus of insulin-like growth factors (IGF-1) by a flexible peptide linker by Dami cell proliferation assay, colony-forming assay, and analysis of platelet in mice to prove our hypothesis. The total number of mice used was 48 in all 4 groups. RESULTS: The fusion proteins were produced in Escherichia coli BL21 (DE3) at up to 26% of the total cell proteins. Subsequent biological activity assays showed that the fusion proteins exhibited higher potency than recombinant human thrombopoietin (TPO). Our results showed that the fusion proteins IGF-1-TMP exhibited higher biological activities than TMP in Dami cell proliferation, human cord blood cell colony-forming assays, and in experiments on acute myeloid radiation sickness mice, which can effectively increase the number of platelets. CONCLUSION: Experiments in mice and biology activity assay, which can effectively increase the number of platelets, indicated that it has a potential role in pharmaceutical applications for the treatment of thrombocytopenia.


Assuntos
Fator de Crescimento Insulin-Like I/farmacologia , Peptídeos/farmacologia , Contagem de Plaquetas , Animais , Sequência de Bases , Proliferação de Células/efeitos dos fármacos , Primers do DNA , Humanos , Fator de Crescimento Insulin-Like I/química , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/química
13.
Sci China Life Sci ; 53(1): 94-100, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20596960

RESUMO

High mammalian gene expression was obtained for more than twenty different proteins in different cell types by just a few laboratory scale stable gene transfections for each protein. The stable expression vectors were constructed by inserting a naturally-occurring 1.006 kb or a synthetic 0.733 kb DNA fragment (including intron) of extremely GC-rich at the 5' or/and 3' flanking regions of these protein genes or their gene promoters. This experiment is the first experimental evidence showing that a non-coding extremely GC-rich DNA fragment is a super "chromatin opening element" and plays an important role in mammalian gene expression. This experiment has further indicated that chromatin-based regulation of mammalian gene expression is at least partially embedded in DNA primary structure, namely DNA GC-content.


Assuntos
Composição de Bases/genética , DNA/genética , Expressão Gênica , Íntrons/genética , Actinas/genética , Animais , Sequência de Bases , Células CHO , Células Cultivadas , Galinhas , Cromatina/genética , Cricetinae , Cricetulus , Mamíferos/genética , Dados de Sequência Molecular , Transfecção
14.
Eur J Nucl Med Mol Imaging ; 34(11): 1832-42, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17541586

RESUMO

PURPOSE: In this study, we evaluated the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced acute and chronic inflammation in living mice by PET imaging of TNF-alpha and integrin alpha(v)beta(3) expression. METHODS: TPA was topically applied to the right ear of BALB/c mice every other day to create the inflammation model. (64)Cu-DOTA-etanercept and (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) were used for PET imaging of TNF-alpha and integrin alpha(v)beta(3) expression in both acute and chronic inflammation. Hematoxylin and eosin staining, ex vivo autoradiography, direct tissue sampling, and immunofluorescence staining were also performed to confirm the non-invasive PET imaging results. RESULTS: The ear thickness increased significantly and the TNF-alpha level more than tripled after a single TPA challenge. MicroPET imaging using (64)Cu-DOTA-etanercept revealed high activity accumulation in the inflamed ear, reaching 11.1 +/- 1.3, 13.0 +/- 2.0, 10.9 +/- 1.4, 10.2 +/- 2.2%ID/g at 1, 4, 16, and 24 h post injection, respectively (n = 3). Repeated TPA challenges caused TPA-specific chronic inflammation and reduced (64)Cu-DOTA-etanercept uptake due to lowered TNF-alpha expression. (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) uptake in the chronically inflamed ears (after four and eight TPA challenges) was significantly higher than in the control ears and those after one TPA challenge. Immunofluorescence staining revealed increased integrin beta(3) expression, consistent with the non-invasive PET imaging results using (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) as an integrin alpha(v)beta(3)-specific radiotracer. Biodistribution and autoradiography studies further confirmed the quantification capability of microPET imaging. CONCLUSION: Successful PET imaging of TNF-alpha expression in acute inflammation and integrin alpha(v)beta(3) expression in chronic inflammation provides the rationale for multiple target evaluation over time to fully understand the inflammation processes.


Assuntos
Imunoglobulina G/metabolismo , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Integrina alfaVbeta3/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Receptores do Fator de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Radioisótopos de Cobre/farmacocinética , Etanercepte , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos BALB C , Especificidade de Órgãos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
15.
Zhong Yao Cai ; 26(12): 855-6, 2003 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-15058203

RESUMO

OBJECTIVE: To identify the genuiness on 5 samples of Bupleurum chinense DC. from cultivating base in Dongfeng County, Jilin Province. METHODS: RAPD was used by 23 primers. RESULTS: The three primers can effectively identify the genuiness of Bupleurum chinense. CONCLUSION: The genuiness identification of Bupleurum chinense can be made with RAPD analysis.


Assuntos
Bupleurum/genética , DNA de Plantas/análise , Plantas Medicinais/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Bupleurum/classificação , Bupleurum/crescimento & desenvolvimento , Primers do DNA , DNA de Plantas/isolamento & purificação , Marcadores Genéticos , Farmacognosia , Plantas Medicinais/crescimento & desenvolvimento , Controle de Qualidade , Especificidade da Espécie
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