Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A

We encapsulated cyclosporine A (CsA) in poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PEG-PLGA) nanoparticles (NPs) by nanoprecipitation of CsA and PEG-PLGA. The resulting CsA/PEG-PLGA-NPs were <100 nm in diameter with a narrow particle size distribution. The NP size could be controlled by tuning the polymer concentration, solvent, or water/solvent ratio during formulation. The PEGylated NPs maintained non-aggregated in salt solution. Solid NPs lyoprotected with bovine serum albumin were prepared for the convenience of storage and transportation. The release kinetics of CsA (55.6% released on Day 1) showed potential for maintaining therapeutic CsA concentrations in vivo. In T-cell assays, both free CsA and CsA/PEG-PLGA-NPs suppressed T-cell proliferation and production of inflammatory cytokines dose dependently. In a mixed lymphocyte reaction assay, the IC50 values for free CsA and CsA/PEG-PLGA-NPs were found to be 30 and 35 ng/mL, respectively. This nanoparticulate CsA delivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency and potentially reduced toxicity

The Novel Therapeutic Effect of Phosphoinositide 3-Kinase-γ Inhibitor AS605240 in Autoimmune Diabetes

Type 1 diabetes (T1D) remains a major health problem worldwide, with a steadily rising incidence yet no cure. Phosphoinositide 3-kinase-γ (PI3Kγ), a member of a family of lipid kinases expressed primarily in leukocytes, has been the subject of substantial research for its role in inflammatory diseases. However, the role of PI3Kγ inhibition in suppressing autoimmune T1D remains to be explored. We tested the role of the PI3Kγ inhibitor AS605240 in preventing and reversing diabetes in NOD mice and assessed the mechanisms by which this inhibition abrogates T1D. Our data indicate that the PI3Kγ pathway is highly activated in T1D. In NOD mice, we found upregulated expression of phosphorylated Akt (PAkt) in splenocytes. Notably, T regulatory cells (Tregs) showed significantly lower expression of PAkt compared with effector T cells. Inhibition of the PI3Kγ pathway by AS605240 efficiently suppressed effector T cells and induced Treg expansion through the cAMP response element-binding pathway. AS605240 effectively prevented and reversed autoimmune diabetes in NOD mice and suppressed T-cell activation and the production of inflammatory cytokines by autoreactive T cells in vitro and in vivo. These studies demonstrate the key role of the PI3Kγ pathway in determining the balance of Tregs and autoreactive cells regulating autoimmune diabetes

Alumina coatings on Ni-based superalloys: the impact of annealing on heavy oil fouling

ABSTRACT: As the sweet crude oil reserves decline, refiners must treat sulfur-rich heavy oil, requiring harsher operating conditions, which are detrimental to process equipment. Application of coatings on critical components protects surfaces against sulfidation, corrosion, and fouling, extends the equipment's lifetime, and reduces the frequency of costly turnarounds. In the present work, we coated Inconel 625 and Inconel 718 substrates with amorphous alumina thin films at room temperature using reactive RF magnetron sputtering. Annealing of the deposited coatings at 800, 900, and 1000 °C increased hardness, improved adhesion, and generated crystalline polymorphs, predominantly γ-Al2O3 at lower temperatures, while α-Al2O3 was present at 1000 °C. The annealed substrates formed thermally grown oxides (TGOs), which interacted with the alumina coatings. The TGOs followed grain boundaries in the case of IN718 and a crater-like pattern on IN625. Annealed substrate precipitates generated columnar-like protrusions responsible for inducing crack propagation, which exhibited TGO formation. After 2 h exposure to heavy oil (containing 0.06 g g−1 sulfur) at 450°C and 11.3 MPa the as-deposited amorphous alumina presented no clear sign of adherent fouling, while the 1000°C annealed crystalline alumina surfaces presented evidence of fouling

Association of Computer Vision Syndrome with Depression/Anxiety among Lebanese Young Adults: The Mediating Effect of Stress.

peer reviewedComputers have become indispensable in daily activities. With this excess use of electronics, computer vision syndrome (CVS), a highly prevalent condition, is associated with various symptoms. Although understanding the relationship between CVS and mental health has been reported, the impact of CVS has not been explored on more than one psychological aspect. We hypothesize that higher CVS symptoms could be associated with higher levels of anxiety and depression, mediated by higher stress. Therefore, the objective of this study was to determine the association between CVS and depression and anxiety among a sample of Lebanese young adults, along with evaluating the mediating effect of stress on these associations. Between August 2020 and April 2021, 749 participants completed an online questionnaire for this cross-sectional study. Females compared to males (Beta = 3.73) and those with CVS compared to those who did not (Beta = 3.14) were significantly associated with more anxiety, whereas having a university level of education compared to secondary or less (Beta = -3.02) was significantly associated with less anxiety. Females compared to males (Beta = 2.55) and those with CVS compared to those without (Beta = 2.61) were significantly associated with more depression, whereas being of an older age (Beta = -0.18) was significantly associated with less depression. Stress partially mediated the association between CVS and anxiety and between CVS and depression. More CVS was significantly associated with more stress (Beta = 3.05). Higher stress was significantly associated with more anxiety (Beta = 0.70) and depression (Beta = 0.71), whereas more CVS was significantly and directly associated with more anxiety (Beta = 3.14) and depression (Beta = 2.61). This study is the first worldwide to evaluate an association between CVS and mental health. Our results serve as a starting point for healthcare providers (psychiatrists and psychologists, most importantly) to look deeper into CVS when looking for reasons behind mental health issues. Further studies are warranted to confirm our results and look for more factors and mediators in such associations

Role of synergy between wear and corrosion in degradation of materials

Tribocorrosion is a term used to describe the material degradation due to the combination of electrochemical and tribological processes. Due to a synergetic effect, the material loss can be larger than the sum of the losses due to wear and corrosion acting separately. In this thesis, the synergy of wear and corrosion was investigated for different types of material, namely the Ti-6Al-4V alloy, the SS316L stainless steel coated with a thin film of Diamond Like Carbon (DLC), and the SS301 stainless steel coated with a thin film of chromium silicon nitride (CrSiN).A tribocorrosion apparatus was designed and constructed to conduct wear experiments in corrosive media. Sliding ball-on-plate configuration was used in this design, where the contact between the ball and the specimen is totally immersed in the test electrolyte. The specimen was connected to a potentiostat to control its electrochemical parameters, namely the potential and the current. Electrochemical techniques were used to control the kinetics of corrosion reactions, and therefore it was possible to assess separately the role of corrosion and wear in the total degradation of material, and to evaluate the synergy between them.For Ti-6Al-4V, it was found that the corrosion and tribocorrosion depend strongly on the structure of the material. The alpha-equiaxed microstructure with fine dispersed beta-phase exhibited the best corrosion resistance. The corrosion resistance was found to decrease when the basal plane was preferentially aligned parallel to the surface, which is attributed to a low resistance to charge transfer in the oxide films formed on this plane. On the other hand, when wear and corrosion were involved simultaneously, the oxide layer protecting the substrate against dissolution was mechanically destroyed leading to a high corrosion rate. It was found that the hardness was the most important factor determining the tribocorrosion behavior of the Ti-6Al-4V alloy; samples with high hardness exhibited less mechanical wear, less wear-enhanced corrosion, and less corrosion-enhanced wear.For DLC coatings, it was found that interface engineering plays a crucial role in the tribocorrosion behavior of DLC films. DLC films with nitrided interface layer (SS\N3h\DLC) were shown to have very poor tribocorrosion resistance; the DLC film delaminated from the substrate after 50 cycles of sliding wear at 9 N load in Ringer's solution. It should be mentioned that a previous study performed at Ecole Polytechnique de Montreal [4] has shown that the same coating resisted 1800 cycles of dry wear at 22 N without delamination. This demonstrates clearly the effect of corrosion on the wear resistance of DLC films. The use of a-SiN:H bond layer between the SS316L substrate and the DLC film improved significantly the tribocorrosion behavior of the coating. This layer acts as a barrier against corrosion reaction; the polarization resistance was 5.76 GO.cm2 compared to 27.5 MO.cm2 and 1.81 MO.cm2 for the DLC-coated SS316L with nitrided interface layer and the bare substrate, respectively.For CrSiN coatings, it was also shown that nitriding treatment of the substrate prior to deposition reduces significantly the tribocorosion resistance of the CrSiN-coated SS301 substrates. This is attributed to the peculiar morphology of the nitrided surface prior to deposition. The high relives at the grain boundaries of the substrate may be the reason for the generation, during sliding wear, of defects in the film, which makes the infiltration of the liquid easier, and consequently leads to the destruction of the CrSiN film

Tribocorrosion test protocols for sliding contacts

ABSTRACT: Tribocorrosion is a term used to refer to material degradation resulting from a combination of tribological and corrosion processes. To understand better the interaction between wear and corrosion, and consequently to develop highly resistant materials, the materials development and testing community is in need of new experimental instruments and testing protocols. In this chapter, we present tribocorrosion rigs where electrochemical and tribological loadings can be applied simultaneously. Tribocorrosion testing protocols for sliding contact are discussed with the emphasis on advantages and disadvantages of using imposed vs free potential measurements. The imposed potential technique creates artificial oxidizing conditions and provides more quantitative data on synergism between wear and corrosion, whereas the free potential technique reproduces more closely the field conditions with less quantitative data