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Our data shed light on molecular mechanisms contributing to the expression of the different dystrophin isoforms, which could be influenced by a change in the function or expression level of the identified RBPs.Tacrine (TAC) was the first FDA approved drug for the treatment of Alzheimer's disease, resulting in increased memory and enhanced cognitive symptoms in patients. However, long-term therapy presents poor patient compliance associated with undesired side effects such as nausea, vomiting and hepatoxicity. LGH447 To improve its therapeutic efficacy and decrease toxicity, the use of nanoparticles could be applied as a possible solution to delivery TAC. In this context, a project has been designed to develop a new nanostructured lipid carrier (NLC) as a delivery system for TAC and conjugate TAC and model amphipathic peptide (MAP) to decrease TAC limitations. Different formulations loaded with TAC and TAC + MAP were prepared using a combination of Compritol 888 ATO as the solid lipid and Transcutol HP as the liquid lipid component. Physical characterization was evaluated in terms of particle size, surface charge, encapsulation efficiency and in vitro drug release studies. Particle size distributions within the nanometer range were obtained with encapsulation efficiencies of 72.4% for the TAC and 85.6% for the TAC + MAP conjugate. Furthermore, cytotoxicity of all NLC formulations was determined against neuroblastoma cell line SH-SY5Y. The optimized TAC delivery system revealed low toxicity suggesting this could be a potential carrier system to deliver TAC. However, TAC + MAP conjugated even encapsulated in the NLC system demonstrated toxicity against the SH-SY5Y cell line.Human immunodeficiency virus 1 (HIV-1) infection is a global health issue since neither a cure nor a vaccine is available. However, the highly active antiretroviral therapy (HAART) has improved the life expectancy for patients with acquired immunodeficiency syndrome (AIDS). Nucleoside reverse transcriptase inhibitors (NRTIs) are in almost all HAART and target reverse transcriptase (RT), an essential enzyme for the virus. Even though NRTIs are highly effective, they have limitations caused by RT resistance. The main mechanisms of RT resistance to NRTIs are discrimination and excision. Understanding the molecular mechanisms for discrimination and excision are essential to develop more potent and selective NRTIs. Using protein X-ray crystallography, we determined the first crystal structure of RT in its post-catalytic state in complex with emtricitabine, (-)FTC or stavudine (d4T). Our structural studies provide the framework for understanding how RT discriminates between NRTIs and natural nucleotides, and for understanding the requirement of (-)FTC to undergo a conformation change for successful incorporation by RT. The crystal structure of RT in post-catalytic complex with d4T provides a "snapshot" for considering the possible mechanism of how RT develops resistance for d4T via excision. The findings reported herein will contribute to the development of next generation NRTIs.Multidrug resistance (MDR) is the main obstacle in anticancer therapy. The use of drug combinations to circumvent tumor resistance is a well-established principle in the clinic. Among the therapeutic targets, glycoprotein-P (P-gp), an energy-dependent transmembrane efflux pump responsible for modulating MDR, is highlighted. Many pharmacological studies report the ability of calcium channel blockers to reverse tumor resistance to chemotherapy drugs. Isolated for the first time from parsley, the phenylpropanoid apiole is described as a potent calcium channel inhibitor. Taking this into account, herein, the ability of apiole to potentiate the action of well-established chemotherapeutics in the clinic, as well as the compound's relationship with the reversal of the resistance phenomenon by blocking P-gp, is reported. The association of apiole with both chemotherapeutic drugs doxorubicin and vincristine resulted in synergistic effect, in a concentration-dependent manner, as evaluated by the concentration reduction index. Molecular docking analysis demonstrated the affinity between apiole and the active site of P-gp, corroborating the inhibitory effect. Moreover, apiole demonstrated druglikeness, according to ADME analysis. In conclusion, apiole possibly blocks the active P-gp site, with strong binding energy, which, in turn, inhibits doxorubicin and vincristine efflux, increasing the antiproliferative response of these chemotherapeutic agents.Candida-associated denture stomatitis (CADS) is a fungal infection affecting 60-65% of denture wearers. Its etiology is complex and multifactorial and often associated with host immunodeficiency. Evidence exists that vitamin D has potential immunomodulatory and anti-inflammatory effects. link2 The aim of this case-control study was to assess the association between vitamin D levels and CADS. The study included 32 complete denture wearers with CADS and 32 sex- and age-matched complete denture wearers without CADS. The patients were clinically examined, and the severity of denture stomatitis was assessed according to Newton's classification scale. The serum vitamin D level was determined via the use of an electrochemiluminescence assay. The vitamin D level in the CADS group and control group was 54.68 ± 17.07 and 56.82 ± 17.75 nmol/L, respectively. There was no significant difference between the groups (p = 0.622). link3 Univariate logistic regression analysis showed that the presence of CADS was not associated with hypovitaminosis D (odds ratio (OR) = 1.44; 95% confidence interval (CI) = 0.37-5.54). It can be concluded that vitamin D is not associated with CADS and does not play a significant role in host susceptibility to CADS. This finding suggests that vitamin D screening is not indicated routinely in patients with Candida-associated denture stomatitis.Fenbendazole (FEN), a broad-spectrum benzimidazole anthelmintic, suppresses cancer cell growth through various mechanisms but has low solubility and achieves low blood concentrations, which leads to low bioavailability. Solubilizing agents are required to prepare poorly soluble drugs for injections; however, these are toxic. To overcome this problem, we designed and fabricated low-toxicity Soluplus® polymeric micelles encapsulating FEN and conducted toxicity assays in vitro and in vivo. FEN-loaded Soluplus® micelles had an average particle size of 68.3 ± 0.6 nm, a zeta potential of -2.3 ± 0.2 mV, a drug loading of 0.8 ± 0.03%, and an encapsulation efficiency of 85.3 ± 2.9%. MTT and clonogenic assays were performed on A549 cells treated with free FEN and FEN-loaded Soluplus® micelles. The in vitro drug release profile showed that the micelles released FEN more gradually than the solution. Pharmacokinetic studies revealed lower total clearance and volume of distribution and higher area under the curve and plasma concentration at time zero of FEN-loaded Soluplus® micelles than of the FEN solution. The in vivo toxicity assay revealed that FEN-loaded Soluplus® micelle induced no severe toxicity. Therefore, we propose that preclinical and clinical safety and efficacy trials on FEN-loaded Soluplus® micelles would be worthwhile.The paper reports a joint experimental/theoretical study on the aging of reactive Al/CuO nanolaminates, investigating both structural modifications and combustion properties of aged systems. We first show theoretically that the long-term storage (over several decades) in ambient temperature marginally affects nanolaminates structural properties with an increase in an interfacial layer of only 0.3 nm after 30 years. Then, we observe that the first thermal aging step occurs after 14 days at 200 °C, which corresponds to the replacement of the natural Al/CuO interfaces by a proper ~11 nm thick amorphous alumina. We show that this aging step does impact the nanolaminates structure, leading, for thin bilayer thicknesses, to a substantial loss of the energetic reservoir considering a stoichiometric Al/CuO stack, the heat of reaction can be reduced by 6-40% depending on the bilayer thickness ranging from 150 nm (40%) to 1 µm (6%). The impact of such thermal aging (14 days at 200 °C) and interfacial modification on the initiation and combustion properties have been evaluated experimentally and theoretically. Varying Al to CuO ratio of nanolaminates from 1 to 3, we show that ignition time of aged systems does not increase over 10% at initiation power densities superior to 15 W·mm-2. In contrast, burn rate can be greatly impacted depending on the bilayer thickness annealing a stoichiometric nanolaminates with a bilayer thickness of 300 nm at 200 °C for 14 days lowers its burn rate by ~25%, whereas annealing a fuel rich nanolaminates with the same bilayer thickness under the same thermal conditions leads to a burn rate decrease of 20%. When bilayer thickness is greater than 500 nm, the burn rate is not really affected by the thermal aging. Finally, this paper also proposes a time-temperature diagram to perform accelerated thermal aging.Acute severe colitis is the major indication for surgery in inflammatory bowel diseases (IBD), and in particular, in ulcerative colitis (UC). A laparoscopic approach for abdominal colectomy is recommended, due to better perioperative and long-term outcomes. However, costs, time-spending, and outcomes are still a topic of improvement. We designed a standardized 10-steps, sequential approach to laparoscopic colectomy, based on the philosophy of the "critical view of safety", with the aim to improve perioperative outcomes (operative duration, estimated blood loss, complications, readmissions, reoperations, and length of postoperative stay). We performed a retrospective cohort study using data from a prospectively maintained clinical database. We included all the consecutive, unselected patients undergoing laparoscopic subtotal colectomy (SCo) for IBD between 2008 and 2019 in a tertiary IBD Italian Centre. Starting from 2015, we regularly adopted the novel Sequential Approach for a Critical-View Colectomy (SACCo) technique. We included 59 (40.6%) patients treated with different laparoscopic approaches, and 86 patients (59.4%) operated on by the SACCo procedure. The mean operating time was significantly shorter for the SACCo group (144 vs. 224 min; p less then 0.0001). The SACCo technique presented a trend to fewer major complications (6.8% vs. 8.3%), less readmissions (2.3% vs. 13.5%; p = 0.01), and shorter postoperative hospital stay (7.2 vs. 8.8 days; p = 0.003). Laparoscopic SACCo-technique is a safe and reproducible surgical approach for acute severe colitis and may improve the outcomes of this demanding procedure.An RFID-based wireless system to measure the evolution of the setting process of cement-based materials is presented in this paper. The system consists of a wireless RFID temperature sensor that works embedded in concrete, and an external RFID reader that communicates with the embedded sensor to extract the temperature measurement conducted by the embedded sensor. Temperature time evolution is a well known proxy to monitor the setting process of concrete. The RFID sensor consisting of an UWB Bow Tie antenna with central frequency 868 MHz, matched to the EM4325 temperature chip through a T-match structure for embedded operation inside concrete is fully characterized. Results for measurements of the full set up conducted in a real-scenario are provided.