Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Epidemiol Infect ; 152: e27, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38282573

RESUMEN

Introduction of African swine fever (ASF) to China in mid-2018 and the subsequent transboundary spread across Asia devastated regional swine production, affecting live pig and pork product-related markets worldwide. To explore the spatiotemporal spread of ASF in China, we reconstructed possible ASF transmission networks using nearest neighbour, exponential function, equal probability, and spatiotemporal case-distribution algorithms. From these networks, we estimated the reproduction numbers, serial intervals, and transmission distances of the outbreak. The mean serial interval between paired units was around 29 days for all algorithms, while the mean transmission distance ranged 332 -456 km. The reproduction numbers for each algorithm peaked during the first two weeks and steadily declined through the end of 2018 before hovering around the epidemic threshold value of 1 with sporadic increases during 2019. These results suggest that 1) swine husbandry practices and production systems that lend themselves to long-range transmission drove ASF spread; 2) outbreaks went undetected by the surveillance system. Efforts by China and other affected countries to control ASF within their jurisdictions may be aided by the reconstructed spatiotemporal model. Continued support for strict implementation of biosecurity standards and improvements to ASF surveillance is essential for halting transmission in China and spread across Asia.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Epidemias , Enfermedades de los Porcinos , Porcinos , Humanos , Animales , Fiebre Porcina Africana/epidemiología , Fiebre Porcina Africana/prevención & control , Brotes de Enfermedades/veterinaria , China/epidemiología , Sus scrofa , Enfermedades de los Porcinos/epidemiología
2.
Int J Mol Sci ; 25(14)2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39063201

RESUMEN

Esophageal cancer ranks the seventh in cancer incidence and the sixth in cancer death. Esophageal squamous cell carcinoma (ESCC) accounts for approximately 90% of the total cases of esophageal cancer. Chemotherapy is the most effective drug-based method for treatment of esophageal cancer. However, severe side effects of traditional chemotherapy limit its treatment efficacy. Targeted chemotherapy can deliver chemotherapeutic drugs to cancer cells and specifically kill these cells with reduced side effects. In the work, the bivalent aptamer-DNA carrier (BAD) was designed by using an ESCC cell-specific aptamer as the recognition molecule and a GC base-rich DNA sequence as the drug carrier. With doxorubicin (Dox) as chemotherapeutic drugs, the bivalent aptamer-DNA-Dox conjugate (BADD) was constructed for targeted killing of ESCC cells. Firstly, the truncated A2(35) aptamer with a retained binding ability was obtained through optimization of an intact A2(80) aptamer and was used to fuse with DNA carrier sequences for constructing the BAD through simple DNA hybridization. The results of gel electrophoresis and flow cytometry analysis showed that the BAD was successfully constructed and had a stronger binding affinity than monovalent A2(35). Then, the BAD was loaded with Dox drugs to construct the BADD through noncovalent intercalation. The results of fluorescence spectra and flow cytometry assays showed that the BADD was successfully constructed and can bind to target cells strongly. Confocal imaging further displayed that the BADD can be specifically internalized into target cells and release Dox. The results of CCK-8 assays, Calcein AM/PI staining, and wound healing assays demonstrated that the BADD can specifically kill target cells, but not control cells. Our results demonstrate that the developed BADD can specifically deliver doxorubicin to target ESCC cells and selectively kill these cells, offering a potentially effective strategy for targeted chemotherapy of ESCC.


Asunto(s)
Aptámeros de Nucleótidos , Doxorrubicina , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Doxorrubicina/farmacología , Doxorrubicina/química , Humanos , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/farmacología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/genética , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Línea Celular Tumoral , Portadores de Fármacos/química , ADN/química , ADN/metabolismo , Apoptosis/efectos de los fármacos
3.
BMC Infect Dis ; 23(1): 242, 2023 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-37072732

RESUMEN

BACKGROUND: Epidemic zoning is an important option in a series of measures for the prevention and control of infectious diseases. We aim to accurately assess the disease transmission process by considering the epidemic zoning, and we take two epidemics with distinct outbreak sizes as an example, i.e., the Xi'an epidemic in late 2021 and the Shanghai epidemic in early 2022. METHODS: For the two epidemics, the total cases were clearly distinguished by their reporting zone and the Bernoulli counting process was used to describe whether one infected case in society would be reported in control zones or not. Assuming the imperfect or perfect isolation policy in control zones, the transmission processes are respectively simulated by the adjusted renewal equation with case importation, which can be derived on the basis of the Bellman-Harris branching theory. The likelihood function containing unknown parameters is then constructed by assuming the daily number of new cases reported in control zones follows a Poisson distribution. All the unknown parameters were obtained by the maximum likelihood estimation. RESULTS: For both epidemics, the internal infections characterized by subcritical transmission within the control zones were verified, and the median control reproduction numbers were estimated as 0.403 (95% confidence interval (CI): 0.352, 0.459) in Xi'an epidemic and 0.727 (95% CI: 0.724, 0.730) in Shanghai epidemic, respectively. In addition, although the detection rate of social cases quickly increased to 100% during the decline period of daily new cases until the end of the epidemic, the detection rate in Xi'an was significantly higher than that in Shanghai in the previous period. CONCLUSIONS: The comparative analysis of the two epidemics with different consequences highlights the role of the higher detection rate of social cases since the beginning of the epidemic and the reduced transmission risk in control zones throughout the outbreak. Strengthening the detection of social infection and strictly implementing the isolation policy are of great significance to avoid a larger-scale epidemic.


Asunto(s)
Epidemias , Humanos , China/epidemiología , Epidemias/prevención & control , Brotes de Enfermedades , Funciones de Verosimilitud , Distribución de Poisson
4.
Anal Chem ; 94(49): 17212-17222, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36459499

RESUMEN

Esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), poses a serious threat to human health. It is urgently needed to develop recognition tools and discover molecular targets for early diagnosis and targeted therapy of esophageal cancer. Here, we developed several DNA aptamers that can bind to ESCC KYSE410 cells with a nanomolar range of dissociation constants by using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). The selected A2 aptamer is found to strongly bind with multiple cancer cells, including several ESCC cell lines. Tissue imaging displayed that the A2 aptamer can specifically recognize clinical ESCC tissues but not the adjacent tissues. Moreover, we identified integrin ß1 as the binding target of A2 through pull-down and RNA interference assays. Meanwhile, molecular docking and mutation assays suggested that A2 probably binds to integrin ß1 through the nucleotides of DA16-DG21, and competitive binding and structural alignment assays indicated that A2 shares the overlapped binding sites with laminin and arginine-glycine-aspartate ligands. Furthermore, we engineered A2-induced targeted therapy for ESCC. By constructing A2-tethered DNA nanoassemblies carrying multiple doxorubicin (Dox) molecules as antitumor agents, inhibition of tumor cell growth in vitro and in vivo was achieved. This work provides a useful targeting tool and a potential molecular target for cancer diagnosis and targeted therapy and is helpful for understanding the integrin mechanism and developing integrin inhibitors.


Asunto(s)
Aptámeros de Nucleótidos , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Aptámeros de Nucleótidos/química , Integrina beta1/metabolismo , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Ligandos , Técnica SELEX de Producción de Aptámeros
5.
J Theor Biol ; 545: 111149, 2022 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-35500676

RESUMEN

The end-of-outbreak declaration is an important part of epidemic control, marking the relaxation or cancellation of prevention and control measures. We propose a probability model to retrospectively quantify the confidence of giving the end-of-outbreak declaration during the COVID-19 epidemic in early 2020 in Wuhan. By using the linear spline, we firstly estimates the time-varying proportion of cases who miss the nonpharmaceutical interventions (NPIs) among all reported cases. Assuming the reproduction numbers being 1.5, 2.0, 3.0, 4.0, 5.0 and 6.0, the respective probability of the end of the COVID-19 outbreak with time after the last reported case can be iteratively computed. Consequently, the varying reproduction numbers produce slightly different increasing patterns of NPI effectiveness, and the end-of-outbreak declarations with 95% confidence are projected consistently earlier than the day when the lockdown was actually lifted. The reason for the timing discrepancy is discussed as well.


Asunto(s)
COVID-19 , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Brotes de Enfermedades/prevención & control , Humanos , Probabilidad , Estudios Retrospectivos , SARS-CoV-2
6.
Theor Biol Med Model ; 18(1): 17, 2021 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-34602095

RESUMEN

Travelers play a role in triggering epidemics of imported dengue fever because they can carry the virus to other countries during the incubation period. If a traveler carrying dengue virus visits open green space and is bitten by mosquitoes, a local outbreak can ensue. In the present study, we aimed to understand the movement patterns of international travelers in Tokyo using mobile phone data, with the goal of identifying geographical foci of dengue transmission. We analyzed datasets based on mobile phone access to WiFi systems and measured the spatial distribution of international visitors in Tokyo on two specific dates (one weekday in July 2017 and another weekday in August 2017). Mobile phone users were classified by nationality into three groups according to risk of dengue transmission. Sixteen national parks were selected based on their involvement in a 2014 dengue outbreak and abundance of Aedes mosquitoes. We found that not all national parks were visited by international travelers and that visits to cemeteries were very infrequent. We also found that travelers from countries with high dengue prevalence were less likely to visit national parks compared with travelers from dengue-free countries. Travelers from countries with sporadic dengue cases and countries with regional transmission tended to visit common destinations. By contrast, the travel footprints of visitors from countries with continuous dengue transmission were focused on non-green spaces. Entomological surveillance in Tokyo has been restricted to national parks since the 2014 dengue outbreak. However, our results indicate that areas subject to surveillance should include both public and private green spaces near tourist sites.


Asunto(s)
Dengue , Animales , Dengue/epidemiología , Brotes de Enfermedades , Prevalencia , Tokio/epidemiología , Viaje
7.
Analyst ; 146(13): 4180-4187, 2021 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-34105524

RESUMEN

Esophageal cancer is the ninth most common cancer and the sixth most common cause of cancer-related death worldwide, and the esophageal squamous cell carcinoma (ESCC) subtype accounts for about 90% of all cases of esophageal cancer globally. Currently, ESCC is usually diagnosed in late stages, and targeted therapy is lacking. Therefore, the development of ESCC-specific recognition molecules for an early detection and targeted treatment of ESCC is urgently needed. Aptamers are an excellent molecular recognition tool with unique advantages. In this manuscript, three aptamers (S2, S3, and S8) specific to ESCC cells were successfully screened via cell-SELEX. The experimental results displayed the high affinities of the three aptamers for target KYSE150 cells with dissociation constants in the nanomolar range. The specificity evaluation showed that S2 only bound target KYSE150 cells, but S3 and S8 were capable of targeting a series of ESCC cells. Moreover, several truncated aptamers were generated through sequence optimization. In particular, an ultrashort aptamer S3-2-3 with only 18 bases was successfully obtained; after labeling with Cy5 dyes, it was feasible for the specific imaging of ESCC tissues. Furthermore, the target types of the selected aptamers were preliminarily identified as membrane proteins, and target proteins could be captured by S3-2-3, which may be useful for biomarker discovery. Therefore, the selected aptamers hold great potential for clinical diagnosis, biomarker discovery, and the targeted therapy of ESCC.


Asunto(s)
Aptámeros de Nucleótidos , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Línea Celular Tumoral , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Humanos , Técnica SELEX de Producción de Aptámeros
8.
Analyst ; 145(7): 2676-2681, 2020 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-32065595

RESUMEN

Highly sensitive and specific detection of rare tumor cells is urgently needed for early tumor diagnosis. Herein, a split aptamer-based dual hybridization chain reaction (dual-HCR) strategy with flow cytometry analysis was developed to meet this purpose. With the split aptamer pair as the recognition unit and HCR as the signal amplification technique, this strategy achieved an improved detection limit as low as 20 cells in 200 µL binding buffer. Meanwhile, this method was highly specific with distinct recognition of the target cells from the control cell and mixed cell samples. Furthermore, we succeeded in the specific detection of the target cells in 50% human serum, demonstrating that this method has great potential in clinical applications. In theory, this strategy can be used to detect different target cells by using different split aptamers. Therefore, this general, sensitive and specific tumor cell detection method may be helpful for early clinical diagnosis and cancer research.


Asunto(s)
Aptámeros de Nucleótidos/química , Neoplasias/patología , Hibridación de Ácido Nucleico/métodos , Aptámeros de Nucleótidos/metabolismo , Línea Celular Tumoral , Citometría de Flujo , Colorantes Fluorescentes/química , Humanos , Microscopía Confocal , Nanoestructuras/química , Neoplasias/diagnóstico , Neoplasias/metabolismo , Oligonucleótidos/química , Oligonucleótidos/metabolismo
9.
Anal Chem ; 90(10): 6131-6137, 2018 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-29696967

RESUMEN

Cell-surface glycosylation contains abundant biological information that reflects cell physiological state, and it is of great value to image cell-surface glycosylation to elucidate its functions. Here we present a hybridization chain reaction (HCR)-based multifluorescence resonance energy transfer (multi-FRET) method for specific imaging of cell-surface glycosylation. By installing donors through metabolic glycan labeling and acceptors through aptamer-tethered nanoassemblies on the same glycoconjugate, intramolecular multi-FRET occurs due to near donor-acceptor distance. Benefiting from amplified effect and spatial flexibility of the HCR nanoassemblies, enhanced multi-FRET imaging of specific cell-surface glycosylation can be obtained. With this HCR-based multi-FRET method, we achieved obvious contrast in imaging of protein-specific GalNAcylation on 7211 cell surfaces. In addition, we demonstrated the general applicability of this method by visualizing the protein-specific sialylation on CEM cell surfaces. Furthermore, the expression changes of CEM cell-surface protein-specific sialylation under drug treatment was accurately monitored. This developed imaging method may provide a powerful tool in researching glycosylation functions, discovering biomarkers, and screening drugs.


Asunto(s)
Transferencia Resonante de Energía de Fluorescencia , Imagen Óptica , Aptámeros de Nucleótidos/química , Línea Celular Tumoral , Glicoconjugados/química , Glicosilación , Células Hep G2 , Humanos , Polisacáridos/química , Polisacáridos/metabolismo , Propiedades de Superficie
10.
Analyst ; 143(15): 3579-3585, 2018 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-29999048

RESUMEN

Light-up aptamers have attracted growing attention due to their advantages of being label-free and having low fluorescence background. In this work, we developed a light-up fluorescence assay for label-free detection of tumor cells based on a bifunctional split aptamer (BFSA) that contained two DNA strands (BFSA-a and BFSA-b). BFSA-a and BFSA-b were constructed by combining aptamers ZY11 and ThT.2-2, which could specifically bind to the tumor cell SMMC-7721 and activate the fluorescence of thioflavin T (ThT). A Helper strand was introduced to hybridize with BFSA-b, and then BFSA-a and BFSA-b were separated if the target cell was absent. Only when the target cell is present can BFSA-a approach and hybridize with BFSA-b due to the 'induced-fit effect', which made the Helper strand dissociate. Then ThT bound to BFSA and the fluorescence of ThT was activated. The results indicated that this fluorescence assay had a good linear response to the target cells in the range of 250-20 000 cells in 100 µL binding buffer; the lowest cell number actually detected was 125 cells in 100 µL buffer. This assay also displayed excellent selectivity and was successfully applied to detect target cells in 20% human serum samples. The design of bifunctional split aptamers realized no-washing, label-free, low-cost, one-step detection of tumor cells, which could generate detectable fluorescence signals just by mixing nucleic acid aptamers and fluorescent reporter molecules with target cells. Such a design of aptamer probes also has the potential to construct stimuli-responsive controlled drug delivery systems.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Colorantes Fluorescentes , Neoplasias/diagnóstico , Células Neoplásicas Circulantes , ADN , Células Hep G2 , Humanos , Células MCF-7 , Espectrometría de Fluorescencia
11.
Anal Chem ; 89(17): 9347-9353, 2017 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-28782924

RESUMEN

Highly sensitive detection of cancer cells with high signal-to-background ratio (SBR) is still urgently needed. Here, a self-assembling activatable probe (SAAP) based on split aptamers was developed to meet this purpose. The SAAP is formed with quenched fluorescence; only when target cells are present would the split aptamers self-assemble together and thus activate fluorescence by intramolecular and intermolecular fluorescence quenching strategies. As proof of concept, a split aptamer pair stemming from an intact aptamer, ZY11, developed by our lab was selected to construct SAAP. Owing to the design of self-assembly and activation strategy, the SBR of our approach could be raised to ∼40 and achieved a very low detection limit of seven target 7721 cells in 100 µL of binding buffer. Meanwhile, one-step detection of target cells was achieved within 15 min without any washing steps and pretreatment, which shows potential for point-of-care detection. Moreover, we succeeded in the specific recognition of target cells in 50% human serum and mixed cell samples, which indicated this strategy had great advantages in detection in complex biological samples. In addition, dual-signal detection was also successfully implemented, which may be helpful for accurate detection of target cells. Therefore, this rapid, facile, specific, and highly sensitive detection method for cancer cells may provide convenience in cancer research and medical diagnosis.


Asunto(s)
Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Neoplasias , Secuencia de Bases , Línea Celular Tumoral , Humanos , Límite de Detección , Oligonucleótidos/química , Espectrometría de Fluorescencia
12.
Theor Biol Med Model ; 14(1): 14, 2017 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-28747188

RESUMEN

BACKGROUND: A large epidemic of cholera, caused by Vibrio cholerae, serotype Ogawa, has been ongoing in Yemen, 2017. To improve the situation awareness, the present study aimed to forecast the cholera epidemic, explicitly addressing the reporting delay and ascertainment bias. METHODS: Using weekly incidence of suspected cases, updated as a revised epidemic curve every week, the reporting delay was explicitly incorporated into the estimation model. Using the weekly case fatality risk as calculated by the World Health Organization, ascertainment bias was adjusted, enabling us to parameterize the family of logistic curves (i.e., logistic and generalized logistic models) for describing the unbiased incidence in 2017. RESULTS: The cumulative incidence at the end of the epidemic, was estimated at 790,778 (95% CI: 700,495, 914,442) cases and 767,029 (95% CI: 690,877, 871,671) cases, respectively, by using logistic and generalized logistic models. It was also estimated that we have just passed through the epidemic peak by week 26, 2017. From week 27 onwards, the weekly incidence was predicted to decrease. CONCLUSIONS: Cholera epidemic in Yemen, 2017 was predicted to soon start to decrease. If the weekly incidence is reported in the up-to-the-minute manner and updated in later weeks, not a single data point but the entire epidemic curve must be precisely updated.


Asunto(s)
Cólera/epidemiología , Predicción , Epidemias , Humanos , Incidencia , Yemen/epidemiología
13.
Analyst ; 140(17): 5992-7, 2015 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-26181902

RESUMEN

Cholangiocarcinoma (CCA) is a very aggressive biliary tract malignancy with no efficient early diagnosis and therapeutics available, so there is a call for effective molecular probes. Herein, we performed cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) to obtain aptamers for the specific recognition of human cholangiocarcinoma QBC-939 cells. By coordinating sequence homology analysis and secondary structure analysis, we successfully obtained two aptamers with dissociation constants (Kd) in the low nanomolar range. A 23 nt truncated sequence was identified after further analysis on the secondary structure. More importantly, because hepatocellular carcinoma SMMC-7721 cells were employed as the control in the counter selection, the obtained aptamers demonstrated excellent specificity to the target cells, and no binding to several other hepatocellular carcinoma cell lines was observed. Moreover, the aptamers were initially found to recognize membrane proteins, giving them great potential in the field of biomarker discovery. These newly generated aptamers may play a key role in the early diagnosis and clinical treatment of CCA.


Asunto(s)
Aptámeros de Nucleótidos/química , Técnica SELEX de Producción de Aptámeros , Aptámeros de Nucleótidos/metabolismo , Secuencia de Bases , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Línea Celular Tumoral , Membrana Celular/química , Membrana Celular/metabolismo , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Citometría de Flujo , Biblioteca de Genes , Humanos , Microscopía Confocal , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Datos de Secuencia Molecular
14.
Anal Chem ; 86(19): 9466-72, 2014 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-25184732

RESUMEN

Separating the specific from the nonspecific bound single-strand DNA (ssDNA) is the most important step to improve the efficiency of selection procedure. However, most cell-SELEX protocols (where SELEX = systematic evolution of ligands by exponential enrichment) use simply washing only, which leads to incomplete separation. It is well-established that ssDNAs can be adsorbed on single-walled carbon nanotubes (SWCNTs). Based on this, herein, we developed a modified cell-SELEX approach termed "SWCNTs-assisted cell-SELEX". In our approach, SWCNTs are applied in the separation step, during which the unbound or the nonspecific ssDNAs are adsorbed onto SWCNTs, while the bound ssDNAs still remain on the cell surface, because of the stronger interaction between ssDNA and target. The cells can then be centrifuged to enrich the specifically binding aptamers. As a proof of concept, two nasopharyngeal carcinoma (NPC) cell lines-CNE2 cell and HONE cell-were used as the target cell and the negative cell, respectively. The result show that it takes only 6 cycles to enrich the aptamer pool through the SWCNTs-assisted cell-SELEX, which is much shorter than 15 cycles in the conventional cell-SELEX, thus improving the screening efficiency. Moreover, the achieved aptamers show high specificity and affinity with CNE2 cells, which are highly attractive for clinical diagnosis and biomedicine applications.


Asunto(s)
Aptámeros de Nucleótidos/química , Separación Celular/métodos , ADN de Cadena Simple/química , Células Epiteliales/química , Nanotubos de Carbono/química , Técnica SELEX de Producción de Aptámeros/métodos , Línea Celular Tumoral , Células Epiteliales/patología , Citometría de Flujo , Biblioteca de Genes , Ensayos Analíticos de Alto Rendimiento , Humanos , Ligandos , Nasofaringe/química , Nasofaringe/patología
15.
Int J Biol Macromol ; 273(Pt 2): 133134, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38876234

RESUMEN

Hepatocyte growth factor receptor (c-Met) is a suitable molecular target for the targeted therapy of cancer. Novel c-Met-targeting drugs need to be developed because conventional small-molecule inhibitors and antibodies of c-Met have some limitations. To synthesize such drugs, we developed a bispecific DNA nanoconnector (STPA) to inhibit c-Met function. STPA was constructed by using DNA triangular prism as a scaffold and aptamers as binding molecules. After c-Met-specific SL1 and nucleolin-specific AS1411 aptamers were integrated with STPA, STPA could bind to c-Met and nucleolin on the cell membrane. This led to the formation of the c-Met/STPA/nucleolin complex, which in turn blocked c-Met activation. In vitro experiments showed that STPA could not only inhibit the c-Met signaling pathways but also facilitate c-Met degradation through lysosomes. STPA also inhibited c-Met-promoted cell migration, invasion, and proliferation. The results of in vivo experiments showed that STPA could specifically target to tumor site in xenograft mouse model, and inhibit tumor growth with low toxicity by downregulating c-Met pathways. This study provided a novel and simple strategy to develop c-Met-targeting drugs for the targeted therapy of cancer.


Asunto(s)
Aptámeros de Nucleótidos , Proliferación Celular , Neoplasias , Proteínas Proto-Oncogénicas c-met , Transducción de Señal , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/metabolismo , Humanos , Animales , Transducción de Señal/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Línea Celular Tumoral , Aptámeros de Nucleótidos/farmacología , Aptámeros de Nucleótidos/química , Nucleolina , Movimiento Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas de Unión al ARN/metabolismo , Fosfoproteínas/metabolismo , Terapia Molecular Dirigida , ADN/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Oligodesoxirribonucleótidos
16.
ACS Pharmacol Transl Sci ; 7(1): 110-119, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38230289

RESUMEN

Receptor tyrosine kinase (RTK) plays a crucial role in cancer progression, and it has been identified as a key drug target for cancer targeted therapy. Although traditional RTK-targeting drugs are effective, there are some limitations that potentially hinder the further development of RTK-targeting drugs. Therefore, it is urgently needed to develop novel, simple, and general RTK-targeting inhibitors with a new mechanism of action for cancer targeted therapy. Here, a cell membrane-anchored RTK-targeting DNA nanoinhibitor is developed to inhibit RTK function. By using a DNA tetrahedron as a framework, RTK-specific aptamers as the recognition elements, and cholesterol as anchoring molecules, this DNA nanoinhibitor could rapidly anchor on the cell membrane and specifically bind to RTK. Compared with traditional RTK-targeting inhibitors, this DNA nanoinhibitor does not need to bind at a limited domain on RTK, which increases the possibilities of developing RTK inhibitors. With the cellular-mesenchymal to epithelial transition factor (c-Met) as a target RTK, the DNA nanoinhibitor can not only induce steric hindrance effects to inhibit c-Met activation but also reduce the c-Met level via lysosome-mediated protein degradation and thus inhibition of c-Met signaling pathways and related cell behaviors. Moreover, the DNA nanoinhibitor is feasible for other RTKs by just replacing aptamers. This work may provide a novel, simple, and general RTK-targeting nanoinhibitor and possess great value in RTK-targeted cancer therapy.

17.
J Phys Chem Lett ; 15(19): 5191-5201, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38717254

RESUMEN

Rechargeable aqueous zinc-ion batteries (RAZIBs) offer low cost, high energy density, and safety but struggle with anode corrosion and dendrite formation. Gel polymer electrolytes (GPEs) with both high mechanical properties and excellent electrochemical properties are a powerful tool to aid the practical application of RAZIBs. In this work, guided by a machine learning (ML) model constructed based on experimental data, polyacrylamide (PAM) with a highly entangled structure was chosen to prepare GPEs for obtaining high-performance RAZIBs. By controlling the swelling degree of the PAM, the obtained GPEs effectively suppressed the growth of Zn dendrites and alleviated the corrosion of Zn metal caused by water molecules, thus improving the cycling lifespan of the Zn anode. These results indicate that using ML models based on experimental data can effectively help screen battery materials, while highly entangled PAMs are excellent GPEs capable of balancing mechanical and electrochemical properties.

18.
Int J Biol Macromol ; 259(Pt 1): 129002, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38176501

RESUMEN

Tumor cell-targeting molecules play a vital role in cancer diagnosis, targeted therapy, and biomarker discovery. Aptamers are emerging as novel targeting molecules with unique advantages in cancer research. In this work, we have developed several DNA aptamers through cell-based systematic evolution of ligands by exponential enrichment (Cell-SELEX). The selected SYL-6 aptamer can bind to a variety of cancer cells with high signal. Tumor tissue imaging demonstrated that SYL-6-Cy5 fluorescent probe was able to recognize multiple clinical tumor tissues but not the normal tissues, which indicates great potential of SYL-6 for clinical tumor diagnosis. Meanwhile, we identified prohibitin 2 (PHB2) as the molecular target of SYL-6 using mass spectrometry, pull-down and RNA interference assays. Moreover, SYL-6 can be used as a delivery vehicle to carry with doxorubicin (Dox) chemotherapeutic agents for antitumor targeted chemotherapy. The constructed SYL-6-Dox can not only selectively kill tumor cells in vitro, but also inhibit tumor growth with reduced side effects in vivo. This work may provide a general tumor cell-targeting molecule and a potential biomarker for cancer diagnosis and targeted therapy.


Asunto(s)
Aptámeros de Nucleótidos , Neoplasias , Humanos , Aptámeros de Nucleótidos/metabolismo , Prohibitinas , Doxorrubicina/farmacología , Neoplasias/tratamiento farmacológico , Biomarcadores , Técnica SELEX de Producción de Aptámeros/métodos , Línea Celular Tumoral
19.
Nat Ecol Evol ; 8(3): 552-563, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38238436

RESUMEN

The geographic expansion of Homo sapiens populations into southeastern Europe occurred by ∼47,000 years ago (∼47 ka), marked by Initial Upper Palaeolithic (IUP) technology. H. sapiens was present in western Siberia by ∼45 ka, and IUP industries indicate early entries by ∼50 ka in the Russian Altai and 46-45 ka in northern Mongolia. H. sapiens was in northeastern Asia by ∼40 ka, with a single IUP site in China dating to 43-41 ka. Here we describe an IUP assemblage from Shiyu in northern China, dating to ∼45 ka. Shiyu contains a stone tool assemblage produced by Levallois and Volumetric Blade Reduction methods, the long-distance transfer of obsidian from sources in China and the Russian Far East (800-1,000 km away), increased hunting skills denoted by the selective culling of adult equids and the recovery of tanged and hafted projectile points with evidence of impact fractures, and the presence of a worked bone tool and a shaped graphite disc. Shiyu exhibits a set of advanced cultural behaviours, and together with the recovery of a now-lost human cranial bone, the record supports an expansion of H. sapiens into eastern Asia by about 45 ka.


Asunto(s)
Fósiles , Cráneo , Humanos , China , Europa (Continente) , Antropología Cultural
20.
Talanta ; 243: 123399, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35325747

RESUMEN

Sialylation plays a vital role in multiple different physiologic processes, aberrant sialylation is highly related to disease development. Especially in cancer development, changed states of specific cell-surface sialylation implies rich cancer-related information. Therefore, it is necessary to image specific cell-surface sialylation for better understanding biological functions of sialylation. To meet this purpose, we designed a DNA dendrimer-assisted fluorescence resonance energy transfer (FRET) strategy in this work. By labeling multiple FRET donors and acceptors on the target molecules through metabolic oligosaccharide engineering (MOE) and targeted recognition of aptamer-tethered DNA dendrimer, the FRET was significantly improved. With the DNA dendrimer-assisted FRET strategy, specific imaging of cell-surface sialylation on SMMC-7721 and CEM cells were successfully achieved. The obtained FRET signal intensity was approximately four times higher than the control without the assistance of DNA dendrimer. Moreover, this method is competent to monitor changed states of PTK7-specific sialylation induced by tunicamycin. The proposed imaging strategy may provide a powerful tool to explore the physiological roles of specific cell-surface sialylation and the related mechanism of diseases.


Asunto(s)
Dendrímeros , Transferencia Resonante de Energía de Fluorescencia , Membrana Celular , ADN , Oligonucleótidos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA