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Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ) that results from autoantibodies against nicotinic acetylcholine receptors (nAchRs) at NMJs. These autoantibodies are mainly originated from autoreactive B cells that bind and destroy nAchRs at NMJs preventing nerve impulses from activating the end-plates of skeletal muscle. Indeed, immune dysregulation plays a crucial role in the pathogenesis of MG. Autoreactive B cells are increased in MG due to the defect in the central and peripheral tolerance mechanisms. As well, autoreactive T cells are augmented in MG due to the diversion of regulatory T (Treg) cells or a defect in thymic anergy leading to T cell-mediated autoimmunity. Furthermore, macroautophagy/autophagy, which is a conserved cellular catabolic process, plays a critical role in autoimmune diseases by regulating antigen presentation, survival of immune cells and cytokine-mediated inflammation. Abnormal autophagic flux is associated with different autoimmune disorders. Autophagy regulates the connection between innate and adaptive immune responses by controlling the production of cytokines and survival of Tregs. As autophagy is involved in autoimmune disorders, it may play a major role in the pathogenesis of MG. Therefore, this mini-review demonstrates the potential role of autophagy and autophagy activators in MG. Abbreviations: Ach, acetylcholine; Breg, regulatory B; IgG, immunoglobulin G; MG, myasthenia gravis; NMJ, neuromuscular junction; ROS, reactive oxygen species; Treg, regulatory T; Ubl, ubiquitin-like [ABSTRACT FROM AUTHOR]

The study planned to estimate biological parameters linked to rheumatoid arthritis (RA) patients, detecting the influence of MTX and biotherapy treatments on these parameters and synthesizing methotrexate bovine serum albumin nanoparticles linked to folate (FA-MTX-BSA NPs) to reduce the overwhelming expression of inflammatory cytokines. Inflammatory parameters showed significant increases in newly diagnosed and MTX-receiving groups while no changes were observed in the biotherapy-maintained group. MTX-loaded BSA nanoparticles were fabricated by the desolvation method and further linked to activated folic acid to obtain FA-MTX-BSA NPs. FA-MTX-BSA NPs were successfully characterized within the nanoscale range using different screening techniques. FA-MTX-BSA NPs showed an in vitro release in a sustained manner. The potential of MTX, MTX-BSA NPs, and FA-MTX-BSA NPs in inducing cytokine level reduction was detected. Significant decreases in interleukin- 1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels were obtained in cultures treated with FA-MTX-BSA NPs compared to the untreated culture in a dose-dependent pattern. Furthermore, FA-MTX-BSA NPs comparing with MTX and MTX-BSA NPs exhibited a significant advanced effect in decreasing cytokines levels. Accordingly, the conjunction of BSA NPs and MTX linked to folate potentially reduced cytokines manifestation in RA. [ABSTRACT FROM AUTHOR]

We investigated the anti-cancer properties of gold nanoparticles loaded TNF- and CALNN peptides, which we proposed as a potential drug delivery system using in vitro and in vivo models. The binding of GNPs-TNF- and GNPs-TNF-CALNN was characterized using a UV, ELISA and SEM analysis. The outcomes demonstrated that a novel drug delivery system had an anti-proliferative activity against breast cancer cell lines through a mechanism of apoptosis induction. In vivo model involved studying the cytotoxic influence of a drug delivery system GNPs, GNPs-TNF-α and GNPs-TNF-α-CALNN when applied to the transplanted AN-3 cell line. tumor sections were examined using microarray. In-vivo studies demonstrated that GNPs alone had less of a growth inhibitory effect on tumors implanted in mice when compared to GNPs-TNF – CALNN combined therapy. The cytotoxic assay showed that GNPs, GNPs-TNF-α and GNPs-TNF-α-CALNN exhibit selective toxicity towards cancer cells, inducing cell apoptosis through activation of caspase-3 and 7, p53 protein. [ABSTRACT FROM AUTHOR]

Titanium dioxide nanoparticles (TiO2 NPs) are photo-active metallic nanoparticles becoming promising agents in modern biomedical applications. Herein, a novel process for the synthesis of TiO2 NPs with high stability was developed by a sol–gel process and to investigate their cytotoxicity and antibacterial activity. Numerous experiments have been performed to confirm the morphologies, compositions, and physicochemical properties of prepared TiO2 NPs, such as field emission scanning electron microscopy, dynamic light scattering, Zeta potential, Fourier transform infrared spectroscopy and X-ray diffraction. MTT assay was applied to assess the cytotoxicity of the prepared nanoparticles. The results indicate that the synthesized nanoparticles' diameter is about 68 nm and contains the anatase phase, in the range of 2θ from 25 to 80 °C. The hydrodynamic radius of nanoparticles is about 140.4 nm, and the zeta potential of nanoparticles is about −44.6 mV. The MTT results have not shown any toxicity; the antibacterial inhibitory effect of TiO2 NPs at 200 mg/mL concentrations exhibited superior antibacterial activity at 15.9 ± 0.1, 14.0 ± 0.1 against Staphylococcus aureus and Escherichia coli, respectively. In conclusion, colloidal solutions with high stability were successfully synthesized, contributing to decreased dimensions and increased antibacterial properties. [ABSTRACT FROM AUTHOR]

Poly-L-lysine-coated superparamagnetic iron oxide nanoparticles (SPIONs-PLL) were prepared and used as a novel-carrier for the transfer of brain-derived neurotrophic factor (BDNF) into neural stem cells (NSCs) under the beneficial influence of an external magnetic field. Pro-BDNF, a gene from human brain cDNA libraries, was obtained by polymerase chain reaction and constructed in a mammalian expression vector (PSecTag2/HygroB). The nanoparticles (NPs) were examined using Fourier transform infrared spectroscopy, zeta potential, and Transmission electron microscopy. From the results, the levels of BDNF among the transfected and untransfected cells were 30.326 ± 5.9 and 5.85 ± 3.11 pg/mL, respectively, as detected by an ELISA method. Moreover, the enhanced green fluorescent protein vector was used to evaluate the gene expression efficiency for SPIONs-PLL as a non-viral carrier in NSCs. This was performed under the influence of a magnetic field and the transfection reagents (such as Lipofectamine 2000), which served as a positive control. The histological analysis revealed that the concentration of intracellular NPs was significantly higher than intercellular NPs. These results suggest that SPIONs-PLL can serve as a novel alternative for the transfection of BDNF-NSCs and could be used in gene therapy. [ABSTRACT FROM AUTHOR]