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owed that the release of IL4+IL13 increased total sulfated glycosaminoglycan content and decreased fibril alignment, which is typically associated with less fibrotic tissue. Together, these results show that hybrid M1/M2 macrophages regulate ECM assembly, and that shifting the balance towards M2 may promote architectural and compositional changes in ECM with enhanced potential for downstream remodeling.How to make the nanoparticles evade immune surveillance and deeply penetrate the tumor tissues is of great importance to maximize the therapeutic efficacy of nanomedicines. Here, a near-infrared (NIR) light-responsive extracellular vesicle as a nanoplatform is developed to realize long circulation in blood, deep penetration in tumor tissues and rapid body elimination after the treatment. Like a "Trojan horse", the nanoplatform is obtained by hiding the anti-tumor soldiers (DOX and 4.2 nm Ag2S quantum dots (QDs)) into the macrophage cell-secreted vesicle through electroporation. The natural composition and tumor targeting activity of the extracellular vesicles enable the nanoplatform to achieve a high accumulation in tumor and the in vivo biodistribution can be monitored by NIR fluorescence imaging of the Ag2S QDs. After the nanomedicines accumulate at the tumor sites, the soldiers will be released from the "Trojan horse" by utilizing the NIR photothermal effect of the Ag2S QDs. The released ultrasmall QDs and DOX can penetrate the whole tumor with a diameter of about 9 mm and effectively kill the tumor cells. Moreover, the inorganic QDs can be rapidly excreted from the body through renal clearance after the treatment to avoid the potential toxicity.Biomaterials with attenuated adverse host tissue reactions, and meanwhile, combining biocompatibility with mimicry of mechanical and biochemical cues of native extracellular matrices (ECM) to promote integration and regeneration of tissues are important for many biomedical applications. Further, the materials should also be tailorable to feature desired application-related functions, like tunable degradability, injectability, or controlled release of bioactive molecules. Herein, a non-covalently assembled, injectable hydrogel system based on oligopeptides interacting with sulphated polysaccharides is reported, showing high tolerability and biocompatibility in immunocompetent hairless mice. Altering the peptide or polysaccharide component considerably varies the in vivo degradation rate of the hydrogels, ranging from a half-life of three weeks to no detectable degradation after three months. The hydrogel with sulphated low molecular weight hyaluronic acid exhibits sustained degradation-mediated release of heparin-binding molecules in vivo, as shown by small animal magnetic resonance imaging and fluorescence imaging, and enhances the expression of vascular endothelial growth factor in hydrogel surrounding. In vitro investigations indicate that M2-macrophages could be responsible for the moderate difference in pro-angiogenic effects. The ECM-mimetic and injectable hydrogels represent tunable bioactive scaffolds for tissue engineering, also enabling controlled release of heparin-binding signalling molecules including many growth factors.We synthesized unique water-soluble synthetic-polymer, styrene-maleic acid copolymer (SMA) conjugated glucosamine (SG); which formed a stable complex with boric acid (BA). This complex had a mean particle size of 15 nm by light scattering, and single peak in gel permeation chromatography. The particles were taken up by tumor cells five times faster than free BA in vitro and liberated BA at acidic tumor pH (5-7). Liberated BA inhibited glycolysis and resulted in tumor suppression in vivo. Intravenously injected SGB-complex did bind with albumin, and plasma half-life was about 8 h in mice, and accumulated to tumor tissues about 10 times more than in normal organs. IC50 of SGB-complex for HeLa cells under pO2 of 6-9% was about 20 μg/ml (free BA equivalent), 150 times more potent than free BA. Neutron irradiation of human oral cancer cells with SGB-complex resulted in 16 times greater cell-killing than that without SGB-complex. In vivo antitumor effect was evaluated after neutron irradiation only once in SCC VII tumor bearing mice and significant tumor suppression was confirmed. These results indicate that SGB-complex is a unique multifunctional anticancer agent with much more potent activity under low pO2 conditions as in large advanced cancers.Neutrophil-mediated drug-delivery systems have gained widespread attention owing to their superior efficacy in cancer therapy. Neutrophils, the most abundant white cells in peripheral blood, are known to migrate to inflamed tumors. Here, we elaborate on a novel strategy to enhance tumor infiltration of neutrophils by photodynamic/photothermal therapy (PDT/PTT) to deliver ibrutinib (IBR) nanocomplexes for cancer immunotherapy. DiR-loading liposomes (DiR-lipos) were administered to induce acute inflammation, and sialic acid (SA) derivative-coated IBR-loading nanocomplexes (SA-2@NCs) were fabricated for targeting activated peripheral blood neutrophils (PBNs). This in vitro and in vivo attempt, therefore, proved the hypothesis that inducing acute inflammation via PDT/PTT could facilitate the migration of PBNs, which could deliver SA-2@NCs into the tumor. The enhanced tumor delivery of SA-2@NCs was accompanied by enhanced antitumor T-cell immune responses in a mouse orthotopic breast cancer model. Our findings indicate that the combination of IBR-mediated immunotherapy with DiR-mediated PDT/PTT bring together two leading novel strategies, taking advantage of their synergistic mechanisms of action for a potent anti-tumor efficacy for breast cancer therapy.
Chronic hypoxia plays an important role in the initiation and progression of chronic renal disease. The pathogenic role of chronic hypoxia in tubulointerstitial injury has been investigated widely, but little is known about acute hypoxia implications in glomerular damage. Proteasome inhibitor In this study, we investigated the effect of chronic hypoxia on transient receptor potential cation channel 6 (TRPC6) and the underlying mechanism in cultured human podocytes.
Fluo-3 was used as a calcium indicator of the OAG-induced receptor operatedcalciumentry (ROCE) and basal [Ca
]i levels were monitored using laser scanning confocal microscope after exposure of cells to chronic hypoxia. 2-aminoethoxydiphenylborane (2-APB), a pharmacological blocker of TRPCs channels, was used to determine the role of TRPC6 in podocytes under chronic hypoxia. The mRNA expression and protein levels of TRPC6 were determined using Real-time RT-PCR and Western Blotting under normoxic and chronic hypoxic conditions. Actin arrangement was analyzed by confocal microscopy using phalloidin staining of F-actin in podocytes.
Here's my website: https://www.selleckchem.com/Proteasome.html
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