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This strategy combined the FRβ amplification effect with the effective delivery of siRNA, is mostly desirable for the AML-targeting therapy.Ulcerative colitis (UC) is an inflammatory condition involving ulcers in colon and rectum. Conventional treatments for colitis confront serious limitations like off target systemic side effects, drug degradation and inactivation, restricted absorption and other complications culminating in poor bioavailability. These limitations necessitate localized drug delivery to inflamed colon such that drug can bypass abrasive gastric surroundings, availing protection form gastric acid and has selective access to colonic mucosa. Therefore, present study was designed to formulate Eudragit-S100 coated 5-amino salicylic acid (5-ASA)-loaded gelatin nanoparticles (NPs) for localized delivery of 5-ASA for treatment of ulcerative colitis. NPs were formulated by nanoprecipitation and solvent evaporation method, had hydrodynamic diameter of 225-250 nm, smooth and spherical surface morphology under TEM, SEM and AFM. Oral administration of NPs ameliorated disease activity indices like fecal occult bleeding, colon length and stool consistency. NPs treatment significantly reduced mast cells infiltration in colon, restored protective mucin layer and appreciably reinstated colonic histoarchitecture. Furthermore, inflammatory biomarkers like TNF-α, IL1-β, COX-2, iNOS, myeloperoxidase and nitrite levels were also significantly reduced by NPs treatment. Overall, results of this study indicate that 5-ASA NPs possessed superior therapeutic efficacy over free 5-ASA in experimental colitis and these results are attributed to their ability to significantly suppress inflammation.Intragenic antimicrobial peptides (IAPs) are internal sequences of proteins with physicochemical similarities to Antimicrobial Peptides (AMPs) that, once identified and synthesized as individual entities, present antimicrobial activity. Many mature proteins encoded by the genomes of virtually any organism may be regarded as inner reservoirs of IAPs, conferring them ample biotechnological potential. However, IAPs may also share shortcomings with AMPs, such as low half-life in biological media and non-specific adsorption in eukaryotic cells. The present manuscript reports a translational approach that encompasses the uncovering of two novel IAPs from human proteins as well as the first results concerning the incorporation and sustained release of one of these peptides from ureasil-polyether hybrid polymeric films. For such, the software Kamal was used to scan putative IAPs in the human proteome, and two peptides, named Hs05 and Hs06, were identified, synthesized, and tested as antimicrobials. Biophysical assays were conducted using model phospholipid vesicles and 1H NMR solution structures in phospholipid micelles were obtained for the IAP Hs05. This peptide was incorporated in a polymeric matrix composed of the ureasil/PPO-PEO-PPO triblock copolymer, and the resulting films were evaluated by atomic force microscopy and imaging mass spectrometry. The release rate of Hs05 from the polymeric matrix was assessed and the antimicrobial activity of Hs05-loaded hybrid polymeric films was evaluated against the bacterium Escherichia coli. This study represents the first steps towards the development of polymeric films enriched with IAPs obtained from the human proteome as sustained release devices for topical application.Development of functional biological substitutes for skin tissue engineering applications has observed several advancements over the past few decades. In this regard, intelligent extracellular matrix (ECM) mimetic scaffolds have recently evolved as a promising paradigm by presenting instructive cues directing cell-matrix communication, tissue remodeling and homeostasis. However, orchestring multitude attributes of skin ECM yet presents an intriguing challenge to be addressed. In the present work, we have developed an in vitro skin scaffold by coating a bio-mimetic ECM cue κ-carrageenan on electrospun nanofibers for the first time. κ-Carrageenan, a natural sulfated algal polysaccharide exhibits close similarity with native glucosaminoglycans (GAGs) of skin ECM. On the other hand, electrospun nanofibers resemble the 3D nano-topographic architecture of ECM. In the coated form, κ-carrageenan could provide the biochemical cues necessary for cellular functions on the nanofibrous scaffold, thereby mimicking the native 3D microenvironment of skin ECM. The nano-architecture of the electrospun matrix is retained in the fabricated scaffold even after coating with κ-carrageenan. The developed biomimetic scaffold significantly supplements adhesion, growth, infiltration, survival and proliferation of fibroblasts. Furthermore, enhanced gene expression and excessive secretion of collagen proteins by fibroblasts communicate a conducive skin ECM micro-environment formation on the algal polysaccharide coated nanofibrous scaffold. Taken together, these findings present a simple yet effective strategy for the fabrication of ECM mimetic scaffold for promising skin tissue engineering applications.Tissue engineering is focusing research effort on search for new biomaterials that might be applied to create artificial urinary conduit. Nevertheless, the demanding biomechanical characteristics necessary for proper conduit function is difficult to be replicated. In this study, we are introducing novel marine biomaterial obtained by decellularization of squid mantle derived from Loligo vulgaris. https://www.selleckchem.com/products/Cediranib.html Squid mantles underwent decellularization according to developed dynamic flow two-staged procedure. Efficacy of the method was confirmed by computational dynamic flow analysis. Subsequently Decellularized Squid Mantle (DSM) underwent extensive histological analysis and mechanical evaluation. Based on gained biomechanical data the computational modelling using finite element method was utilized to simulate behavior of DSM used as a urinary conduit. Taking into account potential application in reconstructive urology, the DSM was then evaluated as a scaffold for urothelial and smooth muscle cells derived from porcine urinary bladder.
Homepage: https://www.selleckchem.com/products/Cediranib.html
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