Randalltroelsen8189

The main goal of our research was to fabricate electrospun scaffolds from three different silk proteins-silk fibroin from Bombyx mori silkworm cocoons and two recombinant spidroins, rS2/12 and rS2/12-RGDS-and to perform a comparative analysis of the structure, biological properties, and regenerative potential of the scaffolds in a full-thickness rat skin wound model. The surface and internal structures were investigated using scanning electron microscopy and scanning probe nanotomography. The structures of the scaffolds were similar. The average fiber diameter of the scaffolds was 315 ± 26 nm, the volume porosity was 94.5 ± 1.4%, the surface-to-volume ratio of the scaffolds was 25.4 ± 4.2 μm-1 and the fiber surface roughness was 3.8 ± 0.6 nm. The scaffolds were characterized by a non-cytotoxicity effect and a high level of cytocompatibility with cells. The scaffolds also had high regenerative potential-the healing of the skin wound was accelerated by 19 days compared with the control. A histological analysis did not reveal any fragments of the experimental constructions or areas of inflammation. Thus, novel data on the structure and biological properties of the silk fibroin/spidroin electrospun scaffolds were obtained.A drug dissolution profile is one of the most critical dosage form characteristics with immediate and controlled drug release. Comparing the dissolution profiles of different pharmaceutical products plays a key role before starting the bioequivalence or stability studies. CX-5461 molecular weight General recommendations for dissolution profile comparison are mentioned by the EMA and FDA guidelines. However, neither the EMA nor the FDA provides unambiguous instructions for comparing the dissolution curves, except for calculating the similarity factor f2. In agreement with the EMA and FDA strategy for comparing the dissolution profiles, this manuscript provides an overview of suitable statistical methods (CI derivation for f2 based on bootstrap, CI derivation for the difference between reference and test samples, Mahalanobis distance, model-dependent approach and maximum deviation method), their procedures and limitations. However, usage of statistical approaches for the above-described methods can be met with difficulties, especially when combined with the requirement of practice for robust and straightforward techniques for data evaluation. Therefore, the bootstrap to derive the CI for f2 or CI derivation for the difference between reference and test samples was selected as the method of choice.Candida is a common agent of infection in humans, which has a wide distribution and is a colonizer fungus of the body, occasionally assuming the role of a pathogen. The type of treatment depends on the site of infection and the clinical condition of the patient. Superficial infections, such as mucosal infections, can be treated with topical medications. So-called alternative therapies have rarely been studied, although the literature records the effectiveness of some treatments, especially as complementary therapy. The aims of this review were to analyze evidence of the anti-Candida inhibitory activity of essential oils of the Citrus, Cupressus, Litsea, and Melaleuca species; in addition to addressing the chemical composition, probable mechanisms of antifungal action and studies of toxicity, cytotoxicity, and genotoxicity were included. The literature from Medline/PubMed, Science Direct, Scopus, Web of Science, and the Brazilian database Periodic Capes was reviewed. Thirty-eight articles were selected, which included two articles on Litsea spp., seven on Cupressus spp., thirteen articles on Citrus spp., and twenty-one articles on Melaleuca spp. In conclusion, this study showed in vitro evidence for the use of essential oils of the plant species evaluated for the treatment of infections caused by different Candida species.Even though antibiotic treatment remains one of the most common tools to handle bacterial infections, the excessive antibiotic concentration at the target site may lead to undesired effects. Aiming at the fabrication of antibiotic-free biomaterials for antibacterial applications, in this work, we propose the synthesis of gallium (III)-chitosan (Ga (III)-CS) complexes with six different gallium concentrations via an in situ precipitation method. Fourier Transform infrared spectroscopy indicated the chelation of chitosan with Ga (III) by peak shifts and changes in the relative absorbance of key spectral bands, while energy-dispersive X-ray spectroscopy indicated the homogenous distribution of the metal ions within the polymer matrix. Additionally, similar to CS, all Ga (III)-CS complexes showed hydrophobic behavior during static contact-angle measurements. The antibacterial property of the complexes against both Gram-negative and Gram-positive bacteria was positively correlated with the Ga (III) concentration. Moreover, cell studies confirmed the nontoxic behavior of the complexes against the human osteosarcoma cell line (MG-63 cells) and mouse embryonic fibroblasts cell line (MEFs). Based on the results of this study, new antibiotic-free antibacterial biomaterials based on Ga (III)-CS can be developed, expanding the scope of CS applications in the biomedical field.Colorectal cancer with peritoneal metastases is currently treated by cytoreductive surgery and locoregional chemotherapeutics. This standard treatment is associated with high morbidity, mortality, and recurrence rate. To augment the existing therapy, we developed a liposome-based delivery system containing 1,2-stearoyl-3-trimethylammonium-propane chloride (DSTAP), a cationic lipid, to localize a toll-like receptor agonist, resiquimod (R848), in the peritoneal cavity (PerC) for enhancing the immune response against cancer that had spread to the PerC. The liposomes delivered by intraperitoneal injection increased peritoneal retention of R848 by 14-fold while retarding its systemic absorption, leading to a 5-fold decreased peak plasma concentration compared to free R848 in mice. Within the PerC, the DSTAP-liposomes were found in ~40% of the dendritic cells by flow cytometry. DSTAP-R848 significantly upregulated interferon α (IFN-α) in the peritoneal fluid by 2-fold compared to free R848, without increasing the systemic level. Combined with oxaliplatin, a cytotoxic agent inducing immunogenic cell death, DSTAP-R848 effectively inhibited the progression of CT26 murine colorectal tumor in the PerC, while the combination with free R848 only showed a mild effect. Moreover, the combination of oxaliplatin and DSTAP-R848 significantly increased infiltration of CD8+ T cells in the PerC compared to oxaliplatin combined with free R848, indicating enhanced immune response against the tumor. The results suggest that DSTAP-R848 exhibits potential in augmenting existing therapies for treating colorectal cancer with peritoneal metastases via immune activation.The aim of this study was to apply molecular epidemiology, antimicrobial surveillance, and PK/PD analysis to guide the antimicrobial treatment of gonococci infections in a region of the north of Spain. Antibiotic susceptibility testing was performed on all isolates (2017 to 2019, n = 202). A subset of 35 isolates intermediate or resistant to at least two antimicrobials were selected to search for resistance genes and genotyping through WGS. By Monte Carlo simulation, we estimated the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the antimicrobials used to treat gonorrhea, both indicative of the probability of treatment success. In total, 2.0%, 6.4%, 5.4%, and 48.2% of the isolates were resistant to ceftriaxone, cefixime, azithromycin, and ciprofloxacin, respectively. Twenty sequence types were identified. Detected mutations were related to antibiotic resistance. PK/PD analysis showed high probability of treatment success of the cephalosporins. In conclusion, multiple populations of N. gonorrhoeae were identified. We can confirm that ceftriaxone (even at the lowest dose 250 mg) and oral cefixime are good candidates to treat gonorrhea. For patients allergic to cephalosporins, ciprofloxacin should be only used if the MIC is known and ≤0.125 mg/L; this antimicrobial is not recommended for empirical treatment.Dry eye disease (DED) is a high prevalent multifactorial disease characterized by a lack of homeostasis of the tear film which causes ocular surface inflammation, soreness, and visual disturbance. Conventional ophthalmic treatments present limitations such as low bioavailability and side effects. Lactoferrin (LF) constitutes a promising therapeutic tool, but its poor aqueous stability and high nasolacrimal duct drainage hinder its potential efficacy. In this study, we incorporate lactoferrin into hyaluronic acid coated liposomes by the lipid film method, followed by high pressure homogenization. Pharmacokinetic and pharmacodynamic profiles were evaluated in vitro and ex vivo. Cytotoxicity and ocular tolerance were assayed both in vitro and in vivo using New Zealand rabbits, as well as dry eye and anti-inflammatory treatments. LF loaded liposomes showed an average size of 90 nm, monomodal population, positive surface charge and a high molecular weight protein encapsulation of 53%. Biopharmaceutical behaviour was enhanced by the nanocarrier, and any cytotoxic effect was studied in human corneal epithelial cells. Developed liposomes revealed the ability to reverse dry eye symptoms and possess anti-inflammatory efficacy, without inducing ocular irritation. Hence, lactoferrin loaded liposomes could offer an innovative nanotechnological tool as suitable approach in the treatment of DED.Native collagen doughs were processed using a syringe-based extrusion 3D printer to obtain collagen scaffolds. Before processing, the rheological properties of the doughs were analyzed to determine the optimal 3D printing conditions. Samples showed a high shear-thinning behavior, reported beneficial in the 3D printing process. In addition, tetrahydrocurcumin (THC) was incorporated into the dough formulation and its effect on collagen structure, as well as the resulting scaffold's suitability for wound healing applications, were assessed. The denaturation peak observed by differential scanning calorimetry (DSC), along with the images of the scaffolds' surfaces assessed using scanning electron microscopy (SEM), showed that the fibrillar structure of collagen was maintained. These outcomes were correlated with X-ray diffraction (XRD) results, which showed an increase of the lateral packaging of collagen chains was observed in the samples with a THC content up to 4%, while a higher content of THC considerably decreased the structural order of collagen. Furthermore, physical interactions between collagen and THC molecules were observed using Fourier transform infrared (FTIR) spectroscopy. Additionally, all samples showed swelling and a controlled release of THC. These results along with the mucoadhesive properties of collagen suggested the potential of these THC-collagen scaffolds as sustained THC delivery systems.Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive cancer that has the highest mortality rate out of all breast cancer subtypes. Conventional clinical treatments targeting ER, PR, and HER2 receptors have been unsuccessful in the treatment of TNBC, which has led to various research efforts in developing new strategies to treat TNBC. Targeted molecular therapy of TNBC utilizes knowledge of key molecular signatures of TNBC that can be effectively modulated to produce a positive therapeutic response. Correspondingly, RNA-based therapeutics represent a novel tool in oncology with their ability to alter intrinsic cancer pathways that contribute to poor patient prognosis. Current RNA-based therapeutics exist as two major areas of investigation-RNA interference (RNAi) and RNA nanotherapy, where RNAi utilizes principles of gene silencing, and RNA nanotherapy utilizes RNA-derived nanoparticles to deliver chemotherapeutics to target cells. RNAi can be further classified as therapeutics utilizing either small interfering RNA (siRNA) or microRNA (miRNA).