RESUMEN
Gemcitabine is a nucleoside analog widely used as an anticancer agent against several types of cancer. Although gemcitabine sometimes shows excellent effectiveness, cancer cells are often poorly responsive to or resistant to the drug. Recently, specific strains or dysbiosis of the human microbiome were correlated with drug reactivity and resistance acquisition. Therefore, we aimed to identify antibiotic compounds that can modulate the microbiome to enhance the responsiveness to gemcitabine. To achieve this, we confirmed the gemcitabine responsiveness based on public data and conducted drug screening on a set of 250 antibiotics compounds. Subsequently, we performed experiments to investigate whether the selected compounds could enhance the responsiveness to gemcitabine. First, we grouped a total of seven tumor cell lines into resistant and sensitive group based on the IC50 value (1 µM) of gemcitabine obtained from the public data. Second, we performed high-throughput screening with compound treatments, identifying seven compounds from the resistant group and five from the sensitive group based on dose dependency. Finally, the combination of the selected compound, puromycin dihydrochloride, with gemcitabine in gemcitabine-resistant cell lines resulted in extensive cell death and a significant increase in cytotoxic efficacy. Additionally, mRNA levels associated with cell viability and stemness were reduced. Through this study, we screened antibiotics to further improve the efficacy of existing anticancer drugs and overcome resistance. By combining existing anticancer agents and antibiotic substances, we hope to establish various drug combination therapies and ultimately improve cancer treatment efficacy.
Asunto(s)
Antibacterianos , Desoxicitidina , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Gemcitabina , Ensayos Analíticos de Alto Rendimiento , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Humanos , Ensayos Analíticos de Alto Rendimiento/métodos , Resistencia a Antineoplásicos/efectos de los fármacos , Línea Celular Tumoral , Antibacterianos/farmacología , Ensayos de Selección de Medicamentos Antitumorales/métodos , Puromicina/farmacología , Antimetabolitos Antineoplásicos/farmacología , Sinergismo Farmacológico , Antineoplásicos/farmacología , Bibliotecas de Moléculas Pequeñas/farmacologíaRESUMEN
The addition of two-dimensional inorganic nanomaterials can effectively enhance the properties of polyethylene (PE). In the present study, a series of high-performance PE/oleic acid (OA)-siloxene nanocomposites were prepared by in situ polymerization using OA-siloxene-supported Ziegler-Natta catalysts. Compared with the conventional Ziegler-Natta catalyst, the polymerization activity of the OA-siloxene-supported Ziegler-Natta catalyst was enhanced to 100 kg/mol-Tiâ¢h, an increase of 56%. The OA-siloxene fillers exhibited excellent dispersion within the PE matrix through the in situ polymerization technique. Compared to pure PE, PE/OA-siloxene nanocomposites containing 1.13 wt% content of OA-siloxene showed 68.3 °C, 126%, 37%, and 46% enhancements in Tdmax, breaking strength, modulus, and elongation at break, respectively.
RESUMEN
Rammed earth in a built environment has vapor diffusion characteristics and humidity control abilities, each of which is respectively attributed to the porous structures and the hydrophilic properties. Indeed, these structures and properties allow for the easy absorbance of water particles, hence affecting the durability of a rammed earth wall. This paper presents the water-repellency method for rammed earth walls, which utilizes siloxane copolymers containing fluorine. The water-repellent properties are investigated by measuring the contact angle, water absorption rate, and compressive strength after spray-coating with the synthesized siloxane copolymers on the surface of the rammed earth specimens under study. The water contact angle of the specimen, coated with a siloxane copolymer containing 10 mol.% of a silane monomer with a fluorine group, is about 140°. The water absorption of the specimen obtained after immersing in water for 24 h is low, at about 3.5 wt.%. In addition, the compressive strength remains more than 80% of the corresponding strength of the specimen which is not immersed in water. It is confirmed that the use of a 10% by volume of the siloxane copolymer containing the fluorine group may enhance the water-repellent performance and economic competitiveness.