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1.
RSC Adv ; 14(12): 8240-8250, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38482069

RESUMEN

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

2.
Anat Rec (Hoboken) ; 299(6): 741-7, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26917449

RESUMEN

Vascular endothelial growth factor-C (VEGF-C) is a key regulator in lymphangiogenesis, and is overexpressed in various malignancies. Integrin α4ß1, a new member of the VEGF-C/VEGF receptor pathway, was found to be overexpressed in melanoma tumors. However, little is known regarding the potential role of integrin α4ß1 in lymphangiogenesis and other solid tumors. The aim of this study was to investigate the expression patterns of integrin α4 and VEGF-C in relation to lymphangiogenesis and clinicopathological parameters in human colon cancer. The expression of integrin α4, VEGF-C, and VEGFR-3 was assessed in 71 human colon cancer tissues and 30 paracancerous normal tissues by immunohistochemical staining. Lymphatic microvessel density (LMVD) was measured after D2-40-labeling, and the correlations among different factors were statistically analyzed. The expression of integrin α4, VEGF-C, VEGFR-3, and LMVD was higher in colon cancer tissues compared with the normal paracancerous colon tissues. There was a positive correlation between the expression of integrin α4 and VEGF-C. Integrin α4 and VEGF-C were significantly associated with the clinicopathological parameters (LMVD, Duke's stage, and lymph node metastasis). Kaplan-Meier analyses indicated that patients with high integrin α4 or VEGF-C expression had significantly shorter overall survival and tumor-free survival time. Multivariate analyses suggested that integrin α4 and VEGF-C may serve as independent prognostic factors for human colon cancer. Both integrin α4 and VEGF-C are involved in lymphangiogenesis and lymphatic metastasis. Our results demonstrated that integrin α4 is a novel prognostic indicator for human colon cancer. Anat Rec, 299:741-747, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Neoplasias del Colon/patología , Integrina alfa4/metabolismo , Linfangiogénesis/fisiología , Metástasis Linfática/patología , Factor C de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/metabolismo , Neoplasias del Colon/mortalidad , Femenino , Humanos , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patología , Masculino , Microvasos/metabolismo , Microvasos/patología , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Regulación hacia Arriba , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven
3.
Org Biomol Chem ; 12(21): 3484-92, 2014 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-24752704

RESUMEN

A series of novel 1,4,7,10-tetraazacyclododecane (cyclen)-based cationic lipids with asymmetric double hydrophobic tails (cholesteryl and long aliphatic chains) were designed and synthesized. Lysine was chosen as a linking moiety in the molecular backbone. The liposomes formed from 8 and dioleoylphosphatidylethanolamine (DOPE) could bind and condense plasmid DNA into nanoparticles under a low N/P ratio. These nano-scaled lipoplexes have low cytotoxicity, and might efficiently transfect A549 cells. In vitro transfection results revealed that all cationic lipids showed a comparable or better transfection efficiency (TE) than commercially available Lipofectamine 2000. The length and saturation degree of the aliphatic chain would affect their gene transfection performance, and the linoleic acid-containing 8e could give the best TE.


Asunto(s)
Colesterol/química , Compuestos Heterocíclicos/síntesis química , Interacciones Hidrofóbicas e Hidrofílicas , Lípidos/síntesis química , Transfección/métodos , Acilación/efectos de los fármacos , Cationes , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Ciclamas , ADN/química , ADN/metabolismo , ADN/ultraestructura , Ensayo de Cambio de Movilidad Electroforética , Etidio/metabolismo , Fluorescencia , Compuestos Heterocíclicos/química , Humanos , Lípidos/química , Liposomas/química , Liposomas/toxicidad , Liposomas/ultraestructura , Tamaño de la Partícula , Fosfatidiletanolaminas/química , Electricidad Estática
4.
Zhong Xi Yi Jie He Xue Bao ; 9(3): 246-51, 2011 Mar.
Artículo en Chino | MEDLINE | ID: mdl-21419076

RESUMEN

Following the development of clinical trials, the methodology of clinical trials has developed a great deal, including randomization method and blinding method, etc. The method of randomization includes simple randomization, stratification randomization, etc. Dynamic randomization is also considered as a method of randomization. Two dynamic randomization methods are introduced in this paper, including a method considering the balance of numbers in each group and a method considering prognostic factors. This paper also demonstrates the procedure of dynamic randomization of the above two methods by simulations and actual examples.


Asunto(s)
Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Proyectos de Investigación , Humanos , Distribución Aleatoria
5.
Genome ; 53(6): 447-57, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20555434

RESUMEN

Sea buckthorn (Hippophae L.) is a woody, outcrossing dioecious pioneer plant, being widely planted as a new berry crop with rich nutritional and medicinal compounds. This long-juvenile and long-lived woody plant can be more difficult to cultivate than other crop plants. Dried-shrink disease (DSD) is a dangerous pathogen that destroys sea buckthorn and halts commercial production. We estimated variability of sequence-related amplified polymorphism (SRAP) markers in 77 accessions of 22 sea buckthorn cultivars to seek markers associated with DSD resistance and help to identify potential breeding cultivars. Seventeen SRAP primer combinations generated 289 bands, with a mean of 17 bands per primer combination. At a Dice coefficient of 0.852, the dendrogram generated with 191 polymorphic bands clustered 73 accessions of Hippophae rhamnoides into 2 groups and 4 accessions of Hippophae salicifolia into 1 group. Eleven SRAP markers (Me1-Em3(600), Me1-Em1(680), Me2-Em1(650), Me2-Em1(950), Me3-Em6(1300), Me2-Em6(320), Me2-Em6(400), Me1-Em2(600), Me1-Em1(1200), Me1-Em1(1700), Me2-Em2(250)) were significantly correlated with DSD resistance (P < 0.001). These markers provide a viable option for breeding programs that select lineages with DSD resistance, especially when no other genetic information, such as linkage maps and quantitative trait loci, are available.


Asunto(s)
Marcadores Genéticos/genética , Hippophae/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Enfermedades de las Plantas/genética , Análisis por Conglomerados , ADN de Plantas/genética , Genoma de Planta/genética , Hippophae/clasificación , Inmunidad Innata/genética , Filogenia , Hojas de la Planta/genética , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Especificidad de la Especie
6.
J Integr Plant Biol ; 51(3): 235-42, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19261066

RESUMEN

We reported previously that the protein SB401 from Solanum berthaultii binds to and bundles both microtubules and F-actin. In the current study, we investigated the regulation of SB401 activity by its phosphorylation. Our experimental results showed that the phosphorylation of SB401 by casein kinase II (CKII) downregulates the activities of SB401, namely the bundling of microtubules and enhancement of the polymerization of tubulin. However, phosphorylation of SB401 had no observable effect on its bundling of F-actin. Further investigation using extract of potato pollen indicated that a CKII-like kinase may exist in potato pollen. Antibodies against CKII alpha recognized specifically a major band from the pollen extract and the pollen extract was able to phosphorylate the SB401 protein in vitro. The CKII-like kinase showed a similar ability to downregulate the bundling of microtubules. Our experiments demonstrated that phosphorylation plays an important role in the regulation of SB401 activity. We propose that this phosphorylation may regulate the effects of SB401 on microtubules and the actin cytoskeleton.


Asunto(s)
Proteínas Asociadas a Microtúbulos/metabolismo , Microtúbulos/metabolismo , Solanum/metabolismo , Actinas/metabolismo , Secuencia de Aminoácidos , Quinasa de la Caseína II/metabolismo , Regulación hacia Abajo , Proteínas Asociadas a Microtúbulos/química , Datos de Secuencia Molecular , Fosforilación , Extractos Vegetales/metabolismo , Polen/citología , Polen/metabolismo , Solanum tuberosum/citología , Solanum tuberosum/metabolismo , Tubulina (Proteína)/metabolismo
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