Zobrazení zdroje stránky Kenneysims2108

Tissue and cellular stiffening is associated with pathologies including fibrosis and cancer. Healthy cells also exhibit a wide range of membrane cortical tensions, which have been studied in the field of mechanobiology. Here, we quantify the mechanosensitivity of the lysis agent the di-rhamnolipid (RHA), which is a bacterially produced biosurfactant. RHA exhibited selective lysis correlated strongly with cortical membrane tension in osteoblasts, smooth muscle cells, fibroblasts, epithelial cells, and erythrocytes. Reducing cortical membrane tension by cytoskeleton inhibitors (cytochalasin D and nocodazole) or osmotic regulators (sucrose, polyethylene glycol, and nonionic surfactants) attenuated the RHA toxicity. The selective toxicity of RHA toward human chronic myeloid leukemia K562 cells over healthy blood cells suggests a potential therapy for blood cancer. Targeted killing of myofibroblasts transformed from either fibroblasts or epithelial cells indicates its antifibrotic effect. Combined, these studies showed the potential for specific targeting of cells with differential mechanical properties rather than chemical or biological pathways.Magnetic, antimicrobial-carrying nanoparticles provide a promising, new and direly needed antimicrobial strategy against infectious bacterial biofilms. Penetration and accumulation of antimicrobials over the thickness of a biofilm is a conditio sine qua non for effective killing of biofilm inhabitants. Simplified schematics on magnetic-targeting always picture homogeneous distribution of magnetic, antimicrobial-carrying nanoparticles over the thickness of biofilms, but this is not easy to achieve. Here, gentamicin-carrying magnetic nanoparticles (MNPs-G) were synthesized through gentamicin conjugation with iron-oxide nanoparticles and used to demonstrate the importance of their homogeneous distribution over the thickness of a biofilm. Diameters of MNPs-G were around 60 nm, well below the limit for reticuloendothelial rejection. MNPs-G killed most ESKAPE-panel pathogens, including Escherichia coli, equally as well as gentamicin in solution. MNPs-G distribution in a Staphylococcus aureus biofilm was dependent on magnetic-field exposure time and most homogeneous after 5 min magnetic-field exposure. Exposure of biofilms to MNPs-G with 5 min magnetic-field exposure yielded not only homogeneous distribution of MNPs-G, but concurrently better staphylococcal killing at all depths than that of MNPs, gentamicin in solution, and MNPs-G, or after other magnet-field exposure times. In summary, homogeneous distribution of gentamicin-carrying magnetic nanoparticles over the thickness of a staphylococcal biofilm was essential for killing biofilm inhabitants and required optimizing of the magnetic-field exposure time. This conclusion is important for further successful development of magnetic, antimicrobial-carrying nanoparticles toward clinical application.The noninvasive and real-time detection of glucose sugar from tears is promising for the early diagnosis and treatment of chronic diseases such as diabetes. However, its realization is a big challenge. A suitable biosensor electrode that can closely fit the eye and be electrochemically sensitive is still unrealized. In this work, nitrogen-doped graphene (N-G) was used as an ophthalmic electrode in a high-performance intraocular biosensor. The use of N-G has been reported elsewhere before as it is highly electroactive and so has a particular use in biosensors. We hereby present a novel procedure for making carboxylated chitosan-functionalized nitrogen-containing graphene (GC-COOH) by using a one-step ball-milling process. This process does not use toxic chemicals, flammable gases, or a high temperature. It is thus particularly easy to perform. The fabricated nanomaterial had a high electroactivity and was easily assembled as a glucose biosensor by the immobilization of glucose oxidase. The thus constructed biosensor has a high sensitivity at 9.7 μA mM-1 cm-2, a broad linear range at 12 mM, and a good detection limit of 9.5 μM. It was able to maintain this activity after a month of storage. We also report the intraocular use of this constructed biosensor. The as-prepared GC-COOH was found to be highly biocompatible to ophthalmologic cells such as corneal epithelial and retinal pigment epithelium cells. No change in the intraocular pressure or the corneal structure was measured in a New Zealand white rabbit model. The as-assembled sensor was worn by the animals for more than 24 h without undue impact. This result confirmed the biosensor's potential for intraocular application in the clinic. Its assembly into a useful sensor shown here has great potential to provide real-time monitoring of glucose levels in tear fluids of patients with high sugar levels.An indicator for cytochrome P450 (CYP-450) enzymes includes CYP-450 which has the most fundamental role in methadone metabolism in the liver. The aim of this study is to design and interface a macromolecular nanodrug system to deliver rifampin (RIF) and methadone (MTD) simultaneously to the liver based on magnetic nanoparticles (MNPs). RIF increases the metabolism of MTD in the liver. In this study, MTD was linked to a magnetic nanocapsule including RIF by a heterocyclic linker. This heterocyclic linker was prepared in five steps. Fourier transform infrared spectroscopy and NMR indicated the synthesis of the heterocyclic linker, scanning electron microscopy and confocal fluorescence microscopy exhibited the morphology of NPs and loading MTD. Atomic force microscopy was applied to indicate the three-dimensional topology of NPs and the conglomeration on them. Magnetization properties of loaded and unloaded NPs were characterized by vibrating-sample magnetometer. These patterns indicated superparamagnetic properties of MNPs therefore these NPs do not retain any magnetism after removal of a magnetic field. [https://www.selleckchem.com/products/bay-61-3606.html BAY613606] In vitro release studies of RIF and MTD by UV-vis measurements in several buffer solutions demonstrated that behavior of drug release is related to pH. The histopathology study was performed on the liver of rats injected with MTD, morphine (MOR), and the prepared drug. Cytotoxicity of the prepared sample on MCF-7 cell line assay was assessed via 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide solution. The histopathology study indicated that the cotreatment of the synthesized drug attenuated hepatic lesions. Delivery of RIF and MTD simultaneously to the liver by MNPs (1) increases MTD metabolism because of increasing CYP-450 enzymes induced by RIF and (2) decreases hepatic lesions via injection of the synthesized drug with cotreatment by MOR.