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Wounds can take longer to heal in diabetic patients, increasing the risk of infections and other complications. The most common wounds in diabetic patients are diabetic foot ulcers, a severe complication associated with diabetes mellitus. click here The United States alone spends $18.7 billion annually on care for these wounds including pain and infection management. If improperly managed, infected lesions may require amputation. The enormous cost associated with wound care and the dire consequences if not cared for properly, emphasize the need to develop strategies to accelerate the healing of diabetic foot wounds. Natural rubber latex (NRL), extracted from Hevea brasiliensis (the rubber tree), has been widely applied as a carrier system for several pharmacologically active compounds. Furthermore, it has been shown to encourage angiogenesis, facilitate cell adhesion, and accelerate wound healing. When NRL dressings are applied to wounds of diabetic patients, exudate release is upregulated. The production of exudate is was improved by the presence of NRL while the keratinocytes benefit from the presence of alginate. The NRL-alginate dressings have great potential to improve diabetic wound care by accelerating the healing process.Bone injuries and fractures generally take a long period to heal itself. To address this problem, bone tissue engineering (BTE) has gained significant research impetus. Among the several techniques used for scaffold fabrication, electrospinning ought to be the most promising technique for the development of the nanostructured scaffolds. The present study was carried out to fabricate an electrospun nanocomposite scaffold for BTE by using gelatin, polycaprolactone (PCL), and nanohydroxyapatite (nHAp). To prepare Gelatin-PCL-nHAp nanocomposite scaffold Gelatin-PCL blend was electrospun and then treated with nHAp (1 wt%) for different time periods. The fabricated nanocomposite scaffold was analysed by field emission scanning electron microscopy (FESEM) to determine the fiber diameter and evaluate the fiber morphology. The Gelatin-PCL-nHAp nanocomposite scaffold-20 min exhibited the average fiber diameter of 615±269 nm and average pore size 4.7±1.04 μm, and also revealed the presence of nHAp particles over the Gelatin-PCL scaffold surface. Further, X-ray diffraction (XRD), Fourier Transform Infrared (FTIR) spectroscopy and thermogravimetric (TG) analysis also indicated the deposition of nHAp over the Gelatin-PCL scaffold surface. MTT assay and DNA quantification showed good viability and significant proliferation of human osteoblasts on Gelatin-PCL-nHAp nanocomposite scaffold. Moreover, cell-scaffold constructs illustrated efficient cellular attachment and adequately spread cells, and it also depicts characteristic polygonal morphology of osteoblasts over the Gelatin-PCL-nHAp nanocomposite scaffold. Thus, the results of in-vitro analysis of electrospun nanocomposite scaffold suggest that the Gelatin-PCL-nHAp scaffold can be a potential candidate for BTE applications.The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. link2 The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug.Engineered silica nanoparticles (SiNP) are emerging materials for medical applications. Evaluating biological responses of specific cells treated with engineered silica nanoparticles is however essential. We synthesized and characterized the physicochemical properties of silica nanoparticles with two different sizes of 10 and 100 nm (10SiNP and 100SiNP) dispersed in cell culture medium. HuH-7, an epithelial-like human hepatoblastoma cell line and SK-HEP-1, a liver sinusoidal endothelial cell line (LSEC) are employed to evaluate their biological responses for the SiNP treatment. Primary human lymphocytes are used to assess genotoxicity recommended by OECD guidelines while erythrocytes are used to assess hemolytic activity. The engineered silica nanoparticles are not able to produce radical species, to alter the mitochondrial membrane potential, and induce any adverse effects on cell proliferation. link3 The colony formation ability of HuH-7 hepatoblastoma cells was not affected following the SiNP treatment. Furthermore, SiNPs do not induce hemolysis of red blood cells and are not genotoxic. These findings suggest that SiNPs regardless of the size, amount, and incubation time are biologically safe vehicles to deliver drugs or genes to the liver.3D biopolymeric scaffolds often lack the biochemical cues and mechanical strength to encourage bone tissue regeneration. Chemical crosslinkers have been extensively used to impart strength, but have been found to be toxic at the site of implantation and possess a lacuna in physical strength. We attempted to address this by engineering a self-crosslinked polymer through the in-situ reduction of Graphene oxide (GO) in a gelatin cryogel (Gel-RGO) using ice as a template to create pores. Superior osteoinductive and antimicrobial properties were further endowed on the cryogel by incorporating silver nanoparticles decorated nanohydroxyapatite in the Gel-RGOAg@Hap(2%) cryogel. The optimized biocompatible cryogel favoured bone cell adhesion and its proliferation. The osteoconductive and osteoinductive potential of the cryogel was confirmed through biomineralization and differentiation of bone cells. In addition, these cryogels showed prolonged antimicrobial activity against S. aureus. This investigation exhibits the achievability/prospect of building up an ideal gelatin platform without the utilization of an outside crosslinking agent via manipulating the conditions of gelation. The superior crosslinking achieved between gelatin and GO, in addition to its ability to support bone formation and prevent infection make this cryogel an attractive candidate for bone tissue engineering applications.Acute myeloid leukemia (AML) is the most universal type and fatal disease of hematological malignancy, with poor outcomes despite chemotherapy and bone marrow transplantations. Benefited from the narrow tissue specificity of folate receptor β (FRβ) aberrantly expressed on hematological linage cell lines, NPs modified with folate acid (FA) has been widely applied for crossing cell membrane barriers in FR-targeted therapies for AML. Thus, the biomimetic nanoparticles (NPs) mediated by FRβ were conducted by an albumin modifier as previously synthesized and cationic liposomes. However, how to further enhance the tumor-targeting and cellular uptake of NPs have been great challenges in cancer therapy. It was reported that FRβ could be selectively augmented by all-trans retinoic acid (ATRA). Herein, we demonstrated the enhanced active tumor-targeting of FA-modified siRNA-loaded biomimetic albumin NPs (Lip-S@FBH) could be achieved by upregulating FRβ expression via ATRA NPs. And the systematic administration of ATRA NPs significantly promoted endocytosis and thereby increased the intracellular concentration of Lip-S@FBH. 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.

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