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STAT3/HIF-1α signaling service mediates peritoneal fibrosis activated by simply large glucose.
The term synergism means that the overall therapeutic benefits should be greater than the sum of the effects of individual agents and that the optimal therapeutic efficacy can be achieved at reduced doses. Micellar systems usually fail to deliver multiple drugs to target sites at synergistic doses and thus are not able to maximize the antitumor efficacy. In the current study, we demonstrate a strategy to coordinate the release of camptothecin (CPT) and α-tocopheryl succinate (TOS) from hybrid micelles for nucleus and mitochondrion interferences. TOS is decorated with cationic triphenylphosphonium (TPP) to promote the targeting capability of TOS-TPP to mitochondria. The combination of CPT and TOS-TPP shows strong synergistism with a combination index of 0.186. Hyaluronic acid (HA) is conjugated with CPT or TOS-TPP via disulfide linkages for tumor cell targeting and intracellular reduction-triggered release. Both conjugates either separately self-assemble into MC and MT micelles, or are blended at different ratcacy and enable significant reduction in effective doses of chemotherapeutic agents.A novel nano-CaCO3 (nCaCO3) particle composite-derived polystyrene (PS) resin was successfully synthesized by a suspension polymerization method. The nCaCO3 reinforced PS material (PS/nCaCO3) possessed a structure with abundant mesopores of high porosity, high specific surface area (828.3 m2 g-1) and large pore volume (1.83 cm3 g-1). It was revealed that the incorporation of nCaCO3 into the PS matrix enhanced both the mechanical strength which can prevent the fragmentation and its adsorption capacity for interleukin-6 (IL-6, MW = 24.0 kDa) from human plasma. The adsorption isotherm could be described by the Langmuir model and classified as S-3 type, showing an IL-6 uptake of up to 25.6 ng g-1 at an equilibrium concentration of about 500 ng L-1. The adsorption capacity for IL-6 of PS/nCaCO3 is not only significantly higher than that of PS (without nCaCO3), but also superior to those of currently available adsorbents that are under clinical studies (e.g., CytoSorb™ towards cytokines). In addition, the PS/nCaCO3 adsorbent also had good hemocompatibility and showed no leakage of nCaCO3 in the plasma in a flowing model system. Therefore, the synthesized PS/nCaCO3 nano-composite has a great potential to be used as an efficient adsorbent for the removal of interleukin-6 (IL-6) from blood of inflammatory and auto-immune disease patients through hemoperfusion.Amyloid fibrillation of proteins is likely a key factor leading to the development of amyloidosis-associated diseases. Inhibiting amyloid fibrillation has become a crucial therapeutic strategy. Water-soluble, fluorescent silicon nanoparticles (SiNPs) have great potential in biomedicine for various therapeutic and diagnostic purposes; however, it is unclear whether SiNPs have the ability to inhibit amyloid fibrillation. Herein, insulin was chosen as a protein model, and SiNPs of varying sizes were synthesized upon UV irradiation. The influence of size and concentration of the SiNPs on insulin fibrillation was investigated, and it has been observed that these variables were crucial in regulating insulin fibrillation. Using an average particle size of 6.6 nm and increasing the concentration of the SiNPs to 5.0 μg mL-1, the Thioflavin T (ThT) fluorescence intensity decreased significantly by 90%, with an increased lag time of 76.8 h, compared to that of the control. Insulin aggregates were short, thin fibrils or clusters when incubated with SiNPs, compared to the long, thick fibrils formed for insulin alone. Additionally, we found that the SiNPs prevent the conformational transition of insulin from its initial structure to β-sheets, and thus inhibit nucleation, which is necessary for the formation of large fibrils. The inhibitory activity is attributed to the interactions between the SiNPs and insulin during the nucleation period. Our results demonstrate that the SiNPs disrupt insulin amyloid fibrillation, and thus, may play a useful role in new therapeutic and diagnostic strategies for amyloid-related disorders.Polyvinylpyrrolidone (PVP) has probably been one of the most utilized pharmaceutical polymers with applications ranging from a blood plasma substitute to nanoparticle drug delivery, since its synthesis in 1939. It is a highly biocompatible, non-toxic and transparent film forming polymer. Although high solubility of PVP in aqueous environment is advantageous, it still poses several problems for some applications in which sustained targeting and release are needed or hydrophobic drug inclusion and delivery systems are to be designed. In this study, we demonstrate that a common dietary phenolic antioxidant, p-coumaric acid (PCA), can be combined with PVP covering a wide range of molar ratios by solution blending in ethanol, forming new transparent biomaterial films with antiseptic and antioxidant properties. PCA not only acts as an effective natural plasticizer but also establishes H-bonds with PVP increasing its resistance to water dissolution. PCA could be released in a sustained manner up to a period of 3 days depending on the PVP/PCA molar ratio. Sustained drug delivery potential of the films was studied using methylene blue and carminic acid as model drugs, indicating that the release can be controlled. Antioxidant and remodeling properties of the films were evaluated in vitro by free radical cation scavenging assay and in vivo on a murine model, respectively. Furthermore, the material resorption of films was slower as PCA concentration increased, as observed from the in vivo full-thickness excision model. Finally, the antibacterial activity of the films against common pathogens such as Escherichia coli and Staphylococcus aureus and the effective reduction of inflammatory agents such as matrix metallopeptidases were demonstrated. Nintedanib solubility dmso All these properties suggest that these new transparent PVP/PCA films can find a plethora of applications in pharmaceutical sciences including skin and wound care.A novel supramolecular multivalent glycosidase inhibitor was constructed based on the amphiphilic deoxynojirimycin derivative FA-DNJ. FA-DNJ self-assembled into spherical assemblies with the diameters between 103 nm and 137 nm under different pH values (pH 2-7) and showed a potent glycosidase effect against α-mannosidase with a Ki value of 0.11 μM, an effect that increased approximately 330-fold compared with that of miglitol. In addition, FA-DNJ exhibited a hypoglycaemic effect in mice.
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