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1.
J Transl Med ; 22(1): 314, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532419

RESUMO

BACKGROUND: Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC. METHODS: Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique. Differential protein expression was then evaluated by univariate analysis (p < 0.05). The expression of the selected potential marker was further verified in BC and adjacent tissues by immunohistochemistry (IHC) and single-cell sequencing. A model was constructed to differentiate BC from HC by LASSO regression and compared to the detection capability of FISH. RESULTS: The univariate analysis revealed significant differences in the expression levels of 40 proteins in the serum (p < 0.05) and 17 proteins in the urine (p < 0.05) between BC patients and HC. Six proteins (AREG, RET, WFDC2, FGFBP1, ESM-1, and PVRL4) were selected as potential BC biomarkers, and their expression was evaluated at the protein and transcriptome levels by IHC and single-cell sequencing, respectively. A diagnostic model (a signature) consisting of 14 protein markers (11 in serum and three in urine) was also established using LASSO regression to distinguish between BC patients and HC (area under the curve = 0.91, PPV = 0.91, sensitivity = 0.87, and specificity = 0.82). Our model showed better diagnostic efficacy than FISH, especially for early-stage, small, and low-grade BC. CONCLUSION: Using the PEA method, we identified a panel of potential protein markers in the serum and urine of BC patients. These proteins are associated with the development of BC. A total of 14 of these proteins can be used to detect early-stage, small, low-grade BC. Thus, these markers are promising for clinical translation to improve the prognosis of BC patients.


Assuntos
Detecção Precoce de Câncer , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Curva ROC , Detecção Precoce de Câncer/métodos , Neoplasias da Bexiga Urinária/patologia , Biomarcadores Tumorais
2.
Analyst ; 149(5): 1473-1480, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38294023

RESUMO

Phosphorescence analyses have attracted broad attention due to their remarkable merits of the elimination of auto-fluorescence and scattering light. However, it remains a great challenge to develop novel materials with uniform size and morphology, stability, long lifetime, and aqueous-phase room temperature phosphorescence (RTP) characteristics. Herein, monodisperse and uniform RTP nanobeads were fabricated by an in situ covalent hybridization of carbon dots (CDs) and dendritic mesoporous silicon nanoparticles (DMSNs) via silane hydrolysis. The formation of Si-O-C and Si-C/N covalent bonds is beneficial for the fixation of vibrations and rotations of the luminescent centers. Specially, the nanopores of DMSNs provide a confined area that can isolate the triplet state of CDs from water and oxygen and thus ensure the occurrence of aqueous-phase RTP with an ultra-long lifetime of 1.195 s (seen by the naked eye up to 9 seconds). Through surface modifying folic acid (FA), CDs@DMSNs can serve as a probe to distinguish different cell lines that feature varying FA receptor expression levels. In addition, taking MCF-7 as the model, highly sensitive and quantitative detection (linear range: 103-106 cells per mL) has been achieved via an RTP probe. Furthermore, their potential applications in cellular and in vivo time-gated phosphorescence imaging have been proposed and demonstrated, respectively. This work would provide a new route to design CD-based RTP composites and promote their further applications in the medical and biological fields.


Assuntos
Dióxido de Silício , Silício , Carbono , Linhagem Celular , Medições Luminescentes
3.
Anal Chem ; 95(23): 8906-8913, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37265323

RESUMO

Developing highly active and sensitive nanozymes for biothiol analysis is of vital significance due to their essential roles in disease diagnosis. Herein, two metal ion-doped carbon dots (M-CDs) with high peroxidase-like activity were designed and prepared for biothiol detection and identification through the colorimetric sensor array technique. The two M-CDs can strongly catalyze the decomposition of H2O2, accompanied by color changes of 3,3',5,5'-tetramethylbenzidine (TMB) from colorless to blue, indicating peroxidase-mimicking activities of M-CDs. Compared with pure carbon dots (CDs), M-CDs exhibited enhanced peroxidase-like activity owing to the synergistic effect between metal ions and CDs. However, due to the strong binding affinity between biothiols and metal ions, the catalytic activities of M-CDs could be inhibited by different biothiols to diverse degrees. Therefore, using TMB as a chromogenic substrate in the presence of H2O2, the developed colorimetric sensor array can form differential fingerprints for the three most important biothiols (i.e., cysteine (Cys), homocysteine (Hcy), and glutathione (GSH)), which can be accurately discriminated through pattern recognition methods (i.e., hierarchical clustering analysis (HCA) and principal component analysis (PCA)) with a detection limit of 5 nM. Moreover, the recognition of a single biothiol with various concentrations and biothiol mixtures was also realized. Furthermore, actual samples such as cells and sera can also be well distinguished by the as-fabricated sensor array, demonstrating its potential in disease diagnosis.


Assuntos
Carbono , Pontos Quânticos , Carbono/química , Peróxido de Hidrogênio , Pontos Quânticos/química , Cisteína , Metais , Peroxidases , Colorimetria/métodos
4.
Int J Mol Sci ; 24(22)2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-38003686

RESUMO

Machine learning has been increasingly utilized in the field of protein engineering, and research directed at predicting the effects of protein mutations has attracted increasing attention. Among them, so far, the best results have been achieved by related methods based on protein language models, which are trained on a large number of unlabeled protein sequences to capture the generally hidden evolutionary rules in protein sequences, and are therefore able to predict their fitness from protein sequences. Although numerous similar models and methods have been successfully employed in practical protein engineering processes, the majority of the studies have been limited to how to construct more complex language models to capture richer protein sequence feature information and utilize this feature information for unsupervised protein fitness prediction. There remains considerable untapped potential in these developed models, such as whether the prediction performance can be further improved by integrating different models to further improve the accuracy of prediction. Furthermore, how to utilize large-scale models for prediction methods of mutational effects on quantifiable properties of proteins due to the nonlinear relationship between protein fitness and the quantification of specific functionalities has yet to be explored thoroughly. In this study, we propose an ensemble learning approach for predicting mutational effects of proteins integrating protein sequence features extracted from multiple large protein language models, as well as evolutionarily coupled features extracted in homologous sequences, while comparing the differences between linear regression and deep learning models in mapping these features to quantifiable functional changes. We tested our approach on a dataset of 17 protein deep mutation scans and indicated that the integrated approach together with linear regression enables the models to have higher prediction accuracy and generalization. Moreover, we further illustrated the reliability of the integrated approach by exploring the differences in the predictive performance of the models across species and protein sequence lengths, as well as by visualizing clustering of ensemble and non-ensemble features.


Assuntos
Aprendizado de Máquina , Proteínas , Reprodutibilidade dos Testes , Proteínas/genética , Sequência de Aminoácidos , Modelos Lineares
5.
Anal Chem ; 94(33): 11514-11520, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35959591

RESUMO

By virtue of the fascinating merits of low cost, rapid screening, and on-site detection, fluorescence lateral flow assays (FLFAs) have attracted considerable attention. Their detection limits are closely associated with the label probes used. The development of high-performance and robust phosphors remains a great challenge. Herein, we presented a new label probe, i.e., fluorescent carbon nanobeads (FCNBs), for FLFAs. Monodispersive, water-soluble, and highly emissive FCNBs were facilely prepared via a hydrothermal carbonization manner. Their abundant amino groups were beneficial for versatile surface functionalization. After being modified by biomolecules, the fabricated FCNB reporter probes were adopted for the construction of lateral flow test strips toward representative foodborne toxins, i.e., aflatoxin B1 (AFB1), and pathogenic bacteria, i.e., Staphylococcus aureus (S. aureus), respectively. The detection limits (0.01 ng/mL for AFB1 and 102 cfu/mL for S. aureus) were about 1 or 2 orders of magnitude lower than most reported methods. Furthermore, the proposed test strips were successfully applied for the quantitative, accurate, and rapid screening of AFB1 and S. aureus in food samples. This work provided a promising label probe for FLFAs and would open the opportunity to exploit a sensing platform by modifying different ligands onto the FCNBs.


Assuntos
Técnicas Biossensoriais , Corantes Fluorescentes , Aflatoxina B1/análise , Técnicas Biossensoriais/métodos , Carbono , Fluorescência , Limite de Detecção , Staphylococcus aureus
6.
Anal Chem ; 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36542541

RESUMO

Antisense peptide nucleic acid (asPNA), an effective antisense drug, has been employed as a gene therapy agent and a useful tool in molecular biology. Gaining control over the delivery of asPNA to target tissues has been a major hindrance to its wide application in clinical practice. A simple and efficient DNA nanoribbon (DNR)-based drug delivery process has been designed in this study that releases the asPNA agent to inhibit oncogenic microRNAs (miRNAs). Furthermore, we demonstrated how the AS1411 aptamer that binds nucleolin on the cell membranes works as a control mechanism capable of identifying target cancer cells and enhancing the enrichment capacity of DNR. With the biodegradability of DNR, we can efficiently initiate the release of asPNA into the cytoplasm, particularly targeting the intended miR-21 and synergistically increasing programmed cell death 4 (PDCD4) expression to enhance cell apoptosis. We assume that this well-defined delivery mechanism will aid in designing antisense site-specific treatments for various diseases, including cancer.

7.
Chemistry ; 28(14): e202104174, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35083795

RESUMO

Carbon dots (CDs) have recently emerged as antibacterial agents and have attracted considerable attention owing to their fascinating merits of small size, facile fabrication, and surface functionalization. Most of them are involved in external light activation or hybridization with other functional nanomaterials. Herein, we present peroxidase-like Cu-doped CDs (Cu-CDs) for in vitro antibacterial applications. The unique peroxidase-mimicking property of the Cu-CDs was demonstrated by tetramethylbenzidine chromogenic assay, electron paramagnetic resonance spectra, and hydroxy radical probe. Escherichia coli and Staphylococcus aureus were chosen as representative gram-negative/positive models against which Cu-CDs exhibited superior antimicrobial activity even at a dosage down to 5 µg/mL. A possible mechanism of action was that the Cu-CDs triggered a catalytic redox reaction of endogenous H2 O2 and glutathione depletion in the bacteria cells, with subsequent oxidative stress and membrane disruption. This work provides a new strategy for the design of microenvironment-responsive antimicrobial nano-agents.


Assuntos
Carbono , Pontos Quânticos , Antibacterianos/farmacologia , Cobre/farmacologia , Estresse Oxidativo , Peroxidase , Peroxidases
8.
J Nanobiotechnology ; 20(1): 63, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35109871

RESUMO

BACKGROUND: Luminescent nanomaterials (LNMs), especially newly-exploited fluorescent carbon-dots (CDs), have demonstrated promising candidates for sunlight harvesting and enhanced photosynthesis efficiency of crops. However, most of the studies focus on the design and synthesis of LNMs and primary metabolism in biomass acceleration, secondary metabolism that closely associated with the quality ingredients of plants is rarely mentioned. RESULTS: UV-absorptive and water-soluble NIR-CDs were harvested via a facile microwave-assisted carbonization method. The effect and regulatory mechanism of NIR-CDs on the secondary metabolism and bioactive ingredients accumulation in Tetrastigma hemsleyanum were explored. A total of 191 differential secondary metabolites and 6874 differentially expressed genes were identified when the NIR-CDs were adopted for enhancing growth of T. hemsleyanum. The phenolic acids were generally improved, but the flavonoids were more likely to decrease. The pivotal differentially expressed genes were involved in biosynthesis of secondary metabolites, flavonoid biosynthesis, porphyrin and chlorophyll metabolism, etc. The gene-metabolite association was constructed and 44 hub genes highly related to quality ingredients accumulation and growth were identified, among which and the top 5 genes of the PPI network might be the key regulators. CONCLUSION: This research provided key regulatory genes and differentially accumulating quality ingredients under NIR-CDs-treatment, which could provide a theoretical basis for expanding the applications of nanomaterial in industrial crop agriculture.


Assuntos
Carbono , Vitaceae , Flavonoides , Fotossíntese , Metabolismo Secundário , Vitaceae/genética
9.
J Orthop Traumatol ; 23(1): 25, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35648304

RESUMO

OBJECTIVE: Identifying biomarkers for early diagnosis of postoperative spinal infection is essential to avoid complications after spine surgery. The presented study evaluated serum levels of procalcitonin (PCT), C-reactive protein (CRP), and soluble CD14 subtype (sCD14-ST) in patients who underwent spinal surgery to assess the diagnosis values of PCT and sCD14-ST. METHODS: Serum levels of PCT, CRP, and sCD14-ST were measured in 490 (289 male/201 female) patients who underwent spinal surgery (SS) before and 1 day after surgery. PCT and sCD14-ST levels of patients diagnosed with postoperative infection (PI) and patients diagnosed with postoperative non-infection (PN) were compared. RESULTS: Serum levels of PCT, CRP, and sCD14-ST were significantly increased after surgery (F = 58.393, P = 0.000). In patients diagnosed as having a PI, serum levels of PCT and sCD14-ST were positively correlated with each other (r = 0.90, P < 0.01) and with operation duration (r = 0.92, 0.88, P < 0.01). Receiver operating characteristic (ROC) models showed that both PCT (AUC = 0.817, optimal cutoff: 0.69 ng/ml, P = 0.000) and sCD14-ST (AUC = 0.824, optimal cutoff: 258.27 pg/ml, P = 0.000) can distinguish PI versus PN patients well. CONCLUSION: Our results demonstrated that serum levels of PCT and sCD14-ST have the potential to be used as a diagnostic markers for postoperative spinal infection.


Assuntos
Receptores de Lipopolissacarídeos , Sepse , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pró-Calcitonina , Curva ROC , Sepse/diagnóstico
10.
J Nanobiotechnology ; 19(1): 260, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454524

RESUMO

BACKGROUND: Fluorescent carbon-dots (CDs) with multifaceted advantages have provided hope for improvement of crop growth. Near infrared (NIR) CDs would be more competitive and promising than short-wavelength emissive CDs, which are not directly utilized by chloroplast. The molecular targets and underlying mechanism of these stimulative effects are rarely mentioned. RESULTS: NIR-CDs with good mono-dispersity and hydrophily were easily prepared by a one-step microwave-assisted carbonization manner, which showed obvious UV absorptive and far-red emissive properties. The chloroplast-CDs complexes could accelerate the electron transfer from photosystem II (PS II) to photosystem I (PS I). NIR-CDs exhibited a concentration-dependent promotion effect on N. benthamiana growth by strengthening photosynthesis. We firstly demonstrated that potential mechanisms behind the photosynthesis-stimulating activity might be related to up-regulated expression of the photosynthesis and chloroplast synthesis related genes, among which PsbP and PsiK genes are the key regulators. CONCLUSION: These results illustrated that NIR-CDs showed great potential in the applications to increase crop yields through ultraviolet light harvesting and elevated photosynthesis efficiency. This work would provide a theoretical basis for the understanding and applications of the luminescent nanomaterials (not limited to CDs) in the sunlight conversion-related sustainable agriculture.


Assuntos
Carbono/química , Corantes Fluorescentes/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Luz , Fotossíntese/efeitos dos fármacos , Fotossíntese/genética , Complexo de Proteína do Fotossistema I/genética , Complexo de Proteína do Fotossistema II/genética , Clorofila , Luminescência , Micro-Ondas , Nanoestruturas/química , Fotossíntese/fisiologia , Fotossíntese/efeitos da radiação , Proteínas de Plantas/genética , Pontos Quânticos , Nicotiana/genética , Nicotiana/crescimento & desenvolvimento , Raios Ultravioleta
11.
BMC Musculoskelet Disord ; 22(1): 381, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33892701

RESUMO

BACKGROUND: Chondroblastoma (CB) is a rare, primary, benign bone tumor that commonly affects men aged 15-20 years. It is usually detected in the epiphysis of the long bones, such as the proximal femur, humerus, and tibia. The patella is an infrequent site. CB with secondary aneurysmal bone cyst (ABC) is extremely rare in the patella, which can be easily confused with other common bone tumors of the patella. Thus, it is necessary to make the right diagnosis to get a good outcome. CASE PRESENTATION: We have presented here the case of a 30-year-old man who was suffering from anterior knee pain for the past 6 months that had aggravated 2 weeks before the presentation. Osteolytic bone destruction in the patella could be detected in both his X-ray and computed tomography (CT) examinations, while the magnetic resonance imaging (MRI) detected a fluid level. Accordingly, secondary ABC was presumed. We diagnosed the condition as giant cell tumor (GCT) with secondary ABC and, accordingly, performed curettage inside the focus region with autogenous bone grafting following the patient's medical history, physical manifestations, results of physical and ancillary examinations, and the disease characteristics. However, the intraoperative and postoperative outcomes indicated that the patient's histopathology was consistent with that of typical CB, suggesting a definitive error in diagnosis. Accordingly, the patient was finally diagnosed with patella CB along with secondary ABC. CONCLUSIONS: Past studies have demonstrated that the 3 commonest bone tumors affecting the patella are GCT, CB, and ABC. CB with secondary ABC can be easily misdiagnosed as GCT with secondary ABC or ABC. Performing incision biopsy or excision biopsy and conducting histological examination may be the most effective method for suspected CB with secondary ABC.


Assuntos
Cistos Ósseos Aneurismáticos , Neoplasias Ósseas , Condroblastoma , Adolescente , Adulto , Cistos Ósseos Aneurismáticos/diagnóstico , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Condroblastoma/complicações , Condroblastoma/diagnóstico por imagem , Condroblastoma/cirurgia , Erros de Diagnóstico , Humanos , Masculino , Patela/diagnóstico por imagem , Patela/cirurgia , Adulto Jovem
12.
Bioconjug Chem ; 31(7): 1708-1723, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32538089

RESUMO

Bacterial infections in wounds often delay the healing process, and may seriously threaten human life. It is urgent to develop wound dressings to effectively detect and treat bacterial infections. Nanoparticles have been extensively used in wound dressings because of their specific properties. This review highlights the recent progress on nanoparticle-based wound dressings for bacterial detection and therapy. Specifically, nanoparticles have been applied as intrinsic antibacterial agents or drug delivery vehicles to treat bacteria in wounds. Moreover, nanoparticles with photothermal or photodynamic property have also been explored to endow wound dressings with significant optical properties to further enhance their bactericidal effect. More interestingly, nanoparticle-based smart dressings have been recently explored for bacteria detection and treatment, which enables an accurate assessment of bacterial infection and a more precise control of on-demand therapy.


Assuntos
Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Bandagens , Nanopartículas Metálicas , Ferimentos e Lesões/terapia , Antibacterianos/uso terapêutico , Portadores de Fármacos , Humanos , Cicatrização , Ferimentos e Lesões/microbiologia
13.
Analyst ; 145(21): 6968-6973, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-32856630

RESUMO

Although some colorimetric sensor arrays have been developed for the identification of Chinese liquors, they usually require the confirmation of volatile markers in the liquors by chromatography and mass spectrometry firstly. Herein, we present a simple colorimetric sensor array to identify various Chinese liquors in the liquid phase without the aid of other analytical techniques. The colorimetric sensor array consists of six commercially available and inexpensive solvatochromic dyes, and the sensing mechanism of this array is based on the response of solvatochromic dyes to their local polarity. On the basis of the colour changes of the sensor array, different Chinese liquors are discerned readily using pattern recognition methods, and the statistical analysis results (i.e., hierarchical clustering analysis and principal component analysis) reveal that the as-fabricated sensor array can distinguish the subtle differences between different liquors from the same winery and the same flavor type. Moreover, the developed sensor array can even distinguish diverse diluted liquors from the pristine ones.

14.
Int Heart J ; 61(1): 115-120, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31956140

RESUMO

Coronary collateral circulation (CCC) plays a crucial role in myocardial blood supply, especially for ischemic myocardium. Previous study has shown that neuregulin-1 is a prominent angiogenic factor in diabetic cardiomyopathy, whereas the relationship between neuregulin-1 and CCC has not been investigated. Thus, we aimed to investigate relationship between circulating neuregulin-1 levels and CCC in stable coronary artery disease patients.Coronary artery disease patients with a stenosis of ≥ 90% as evidenced by coronary angiography were included in our study. According to the Rentrop-Cohen classification, coronary collateral degree was graded as 1 to 4. Patients with collateral degree grade 0 or 1 were enrolled in poor CCC group, whereas patients with grade 2 or 3 were enrolled in good CCC group.Plasma neuregulin-1 level was significantly increased in good collateral group and positively related to Rentrop grade (P < 0.01). Multivariate regression analysis and ROC (receiver operating characteristic curve) revealed that plasma neuregulin-1 could predict CCC status effectively.Increased plasma neuregulin-1 level was related to better CCC in patients with coronary artery disease. Neuregulin-1 was an independent and reliable predictor for good coronary collateral development and provided a potential therapeutic strategy to reduce myocardial ischemia injury.


Assuntos
Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Neuregulina-1/sangue , Idoso , Circulação Colateral , Angiografia Coronária , Doença da Artéria Coronariana/metabolismo , Circulação Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Regulação para Cima
15.
Med Sci Monit ; 23: 4132-4140, 2017 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-28844074

RESUMO

BACKGROUND Leptocarpin (LTC) has drawn much attention for suppressing tumor growth or reducing inflammation. However, the effect of LTC on osteosarcoma has rarely been reported. Our object was to determine whether LTC suppresses MG63 cell proliferation, migration, and invasion, and whether type-1 insulin-like growth factor receptor (IGF-1R) is one of the targets in LTC suppressing osteosarcoma. MATERIAL AND METHODS Cytotoxicity of LTC was performed by use of a cell-counting kit-8 (CCK-8). RNA interference (RNAi) or pEABE-bleo IGF-1R plasmid were used for silencing or overexpressing IGF-1R, Western blot (WB) analysis was used for IGF-1R expression, CCK-8 for proliferation, and transwell assay for migration and invasion. RESULTS LTC (23.533 µM) treatment for 48 h was taken as the 50% inhibiting concentration (IC50), which significantly (P<0.05) suppressed MG63 cells proliferation, migration, and invasion. LTC (IC50) obviously inhibited IGF-1R expression in MG63 cells, with similar effect to small interfering RNA (siRNA), while pEABE-bleo IGF-1R transfection overexpressed IGF-1R. siRNA silencing IGF-1R suppressed MG63 cells proliferation, migration, and invasion, while pEABE-bleo IGF-1R transfection was significantly (P<0.05) promoted. With or without siRNA or pEABE-bleo IGF-1R transfection, LTC (IC50) suppressed MG63 cells proliferation, migration, and invasion. The effect of LTC (IC50) combined with siRNA on suppressing MG63 cells proliferation, migration, and invasion was more obvious, while the effect of LTC (IC50) combined with pEABE-bleo IGF-1R transfection was less significant (P<0.05). CONCLUSIONS LTC suppressed osteosarcoma proliferation, migration, and invasion by inhibiting IGF-1R expression. IGF-1R is one of the targets in LTC suppressing osteosarcoma.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Receptores de Somatomedina/antagonistas & inibidores , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Interferência de RNA , RNA Interferente Pequeno/genética , Receptor IGF Tipo 1 , Receptores de Somatomedina/metabolismo , Transdução de Sinais
16.
Int J Cancer ; 138(1): 74-86, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26148677

RESUMO

The L-plastin gene is involved in the invasion and metastasis of prostate cancer. However, the molecular mechanisms underlying L-plastin transcription are unclear. We hypothesize that the occurrence of polymorphic genetic variations in the L-plastin promoter might affect an individual's susceptibility to prostate cancer. In this study, we identified a single nucleotide polymorphism (SNP) at position -1,687 in the L-plastin promoter by genotype sequencing. The SNP -1,687 showed different transcriptional activity in the luciferase assay in vitro. The TRANSFAC software was applied to predict the multiple cis-elements, and luciferase assay was used to further identify the L-plastin regulatory region. We performed EMSAs, supershift assays and ChIP-qPCR demonstrated that the transcriptional suppressor NKX3.1 binds to the SNP site of the L-plastin promoter. SNP -1,687 (T/T) led to an increase in the affinity of NKX3.1 for L-plastin promoter, resulted in lower levels of L-plastin RNA and protein expression. Furthermore, we collected and sequenced samples from 640 individuals (372 prostate cancer patients and 268 healthy controls) from 2000 to 2013. The results showed that SNP -1,687 (T/T) occurred more frequently in the healthy individuals than that in the prostate cancer patients compared to SNP -1,687 (C/C). Similarly, SNP -1,687 (T/T) genotype occurred more frequently compared to SNP -1,687 (C/C) genotype in the patients with low and moderately differentiated tumors. In conclusion, SNP -1,687, located in the NKX3.1 binding site within the L-plastin promoter, might reduce the expression of L-plastin and potentially decrease the tumorigenesis and progression of prostate cancer. This SNP could be a potential prognostic factor for prostate cancer.


Assuntos
Sítios de Ligação , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Glicoproteínas de Membrana/genética , Proteínas dos Microfilamentos/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Fatores de Transcrição/metabolismo , Alelos , Estudos de Casos e Controles , Linhagem Celular Tumoral , Frequência do Gene , Técnicas de Silenciamento de Genes , Genótipo , Proteínas de Homeodomínio/genética , Humanos , Masculino , Razão de Chances , Neoplasias da Próstata/patologia , Ligação Proteica , Análise de Sequência de DNA , Fatores de Transcrição/genética , Ativação Transcricional
17.
Nature ; 461(7260): 74-7, 2009 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-19727196

RESUMO

We live in a macroscopic three-dimensional (3D) world, but our best description of the structure of matter is at the atomic and molecular scale. Understanding the relationship between the two scales requires a bridge from the molecular world to the macroscopic world. Connecting these two domains with atomic precision is a central goal of the natural sciences, but it requires high spatial control of the 3D structure of matter. The simplest practical route to producing precisely designed 3D macroscopic objects is to form a crystalline arrangement by self-assembly, because such a periodic array has only conceptually simple requirements: a motif that has a robust 3D structure, dominant affinity interactions between parts of the motif when it self-associates, and predictable structures for these affinity interactions. Fulfilling these three criteria to produce a 3D periodic system is not easy, but should readily be achieved with well-structured branched DNA motifs tailed by sticky ends. Complementary sticky ends associate with each other preferentially and assume the well-known B-DNA structure when they do so; the helically repeating nature of DNA facilitates the construction of a periodic array. It is essential that the directions of propagation associated with the sticky ends do not share the same plane, but extend to form a 3D arrangement of matter. Here we report the crystal structure at 4 A resolution of a designed, self-assembled, 3D crystal based on the DNA tensegrity triangle. The data demonstrate clearly that it is possible to design and self-assemble a well-ordered macromolecular 3D crystalline lattice with precise control.


Assuntos
DNA/química , Desenho de Fármacos , Conformação de Ácido Nucleico , Sequência de Bases , Cristalização , Cristalografia por Raios X , DNA/genética , Dados de Sequência Molecular
18.
Nano Lett ; 13(2): 793-7, 2013 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-23323601

RESUMO

Designed self-assembled DNA crystals consist of rigid DNA motifs that are held together by cohesive sticky-ended interactions. A prominent application of such systems is that they might be able to act as macromolecular hosts for macromolecular guests, thereby alleviating the crystallization problem of structural biology. We have recently demonstrated that it is indeed possible to design and construct such crystals and to determine their structures by X-ray diffraction procedures. To act as useful hosts that organize biological macromolecules for crystallographic purposes, maximizing the resolution of the crystals will maximize the utility of the approach. The structures reported so far have diffracted only to about 4 Å, so we have examined two factors that might have impact on the resolution. We find no difference in the resolution whether the DNA is synthetic or PCR-generated. However, we find that the presence of a phosphate on the 5'-end of the strands improves the resolution of the crystals markedly.


Assuntos
DNA/química , Nanopartículas/química , Fosfatos/química , Cristalografia por Raios X , DNA/síntese química , Modelos Moleculares
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(1): 221-5, 2014 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-24783565

RESUMO

The logical range of laser power density and optimum laser power density were explored for multi-element analysis of pulverized coal flow with laser-induced breakdown spectroscopy in the present paper. The range of laser energy was chosen from 20 to 160 mJ in the experiment. Pulverized coal less than 200 microm in diameter of particles fell freely through feeder outlet and the rate of flow was controlled by screw feeder. Emissions were collected with pulse laser at 1 064 nm focusing on pulverized coal flow and plasma was generated. The intensity and cause of fluctuation of emission spectra at various laser energy levels were studied. A suitable range of laser power density is from 14.4 to 34.4 GW x cm(-2), and the optimum laser power density is 19.5 GW x cm(-2) for the determination of pulverized coal flow with LIBS.

20.
Pak J Pharm Sci ; 27(5 Suppl): 1695-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25262521

RESUMO

This paper aims to study the recovery function of two drugs combination on rat sciatic nerve injury regeneration model. Sixty rats were divided into groups randomly and averagely. All animals after dividing left sciatic nerve were given epineurium-interrupted suture for constructing peripheral nerve injury model. Muscle on operation side in medication administration team was injected 0.5 ml drug while the contract group was given equal amount of normal saline. Sciatic nerve function evaluation and nerve electrophysiology index detection were conducted after operation at fixed period. We drew materials for morphological observation 12 weeks after operation. The results showed that group with independent administration of nerve growth factor (NGF) and nimodipine (ND) in large dose was superior than group in small dose in nerve electro physiology index (P<0.05) and group with combination administration of NGF and ND in large dose was also superior than group in small dose (P<0.05). In addition, regeneration effect of combination administration group was better than that of independent administration group when using same dose. The larger the dose was, the better the effect was. We can conclude that two-drug combination can promote recovery function on rat sciatic nerve injury regeneration model.


Assuntos
Fator de Crescimento Neural/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Nimodipina/administração & dosagem , Neuropatia Ciática/tratamento farmacológico , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , Masculino , Ratos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiologia , Neuropatia Ciática/patologia , Neuropatia Ciática/fisiopatologia
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