Harnessing the therapeutic potential of mesenchymal stem/stromal cell-derived extracellular vesicles as a novel cell-free therapy for animal models of multiple sclerosis.

Multiple sclerosis (MS) is a chronic, neuroinflammatory, and demyelinating disease of the central nervous system (CNS). Current treatments offer only limited relief from symptoms, and there is no cure. Mesenchymal stem/stromal cells (MSCs) have demonstrated therapeutic potential for MS. However, their clinical application faces challenges, including immune rejection and the potential for tumor formation. Recent studies suggest that MSCs exert their effects through extracellular vesicles (EVs) released from the cells, rather than direct cellular engraftment or differentiation. This discovery has sparked interest in the potential of MSC-derived EVs as a cell-free therapy for MS. This review explores the existing literature on the effects of MSC-EVs in animal models of MS. Administration of MSC-EVs from various tissue sources, such as bone marrow, adipose tissue, and umbilical cord, was found to reduce clinical scores and slow down disease progression in experimental autoimmune encephalomyelitis (EAE), the primary mouse model of MS. The mechanisms involved immunomodulation through effects on T cells, cytokines, CNS inflammation, and demyelination. Although the impact on CNS repair markers remained unclear, MSC-EVs exhibited the potential to modulate neuroinflammation and suppress harmful immune responses in EAE. Further studies are still required, but MSC-EVs demonstrate promising therapeutic effects for MS and warrant further exploration as a novel treatment approach.

The potential effect of silver nanoparticles synthesized with Coffea arabica green seeds on Leishmania major proliferation, cytotoxicity activity, and cytokines expression level.

The goal of this study was to analyze the antileishmanial and antibacterial activity of Coffea arabica green seed biosynthesize silver nanoparticles (C. arabica AgNPs), as well as cytotoxicity and cytokine gene expression. UV-vis spectroscopy, FTIR, and FESEM methods used to examine the C. arabica AgNPs. MTT test was used to assess the antileishmanial and cytotoxicity effects. The gene expression level was assessed in NPs-treated J774 cells by qPCR. The synthesized C. arabica AgNPs were in the size range of 20-70 nm, through FESEM pictures. The IC50 values of the NPs were 65. 4 and 47.70 µg/mL against promastigotes and amastigotes of Leishmania major, but these values were 580.1 and 171.1 µg/mL for Glucantime® as the control drug. C. arabica AgNPs represented a significant increase in IL-12P40, as a Th1 cytokine, in comparison to Glucantime® at high concentrations (P < 0.01), whilst IL-10 expression level showed a significant reduction between NPs-treated and Glucantime®-treated macrophages at 250-1000 µg/mL concentrations (P < 0.001). Moreover, the NPs were cytotoxic on cancer cell lines of Hek293, MCF7, and A172 with the CC50 values of 437.2, 116.8, and 72.9 µg/mL, respectively. It showed a significant effect of these NPs against A172 (P < 0.001). Also, the lowest MIC values of the NPs were obtained for Bacillus subtilis and Staphylococcus aureus (204 µg/mL). According to the antileishmanial, anticancer, and antibacterial activity of these NPs, it can considered a bio-agent drug in the future in endemic countries.

In vitro and in vivo therapeutic potentials of 6-gingerol in combination with amphotericin B for treatment of Leishmania major infection: Powerful synergistic and multifunctional effects.

The ongoing conventional drugs for leishmaniasis treatment are insufficient. The present study aimed to assess 6-gingerol alone and in combination with amphotericin B on Leishmania major stages using experimental and in vivo murine models. Here, arrays of experimental approaches were designed to monitor and evaluate the 6-gingerol potential therapeutic outcomes. The binding affinity of 6-gingerol and IFN-γ was the basis for docking conformations. 6-Gingerol combined with amphotericin B represented a safe mixture, extremely leishmanicidal, a potent antioxidant, induced a remarkable apoptotic index, significantly increased the expression of the Th1-related cytokines (IL-12p40, IFN-γ, and TNF- α), iNOS, and transcription factors (STAT1, c-Fos, and Elk-1). In contrast, the expression of the Th2-related cytokines was significantly downregulated (p < 0.001). This combination was also potent when the lesion appearance was evaluated following three weeks of treatment. The histopathological and immunohistochemical patterns of the murine model represented clusters of CD4+ and CD8+ T lymphocytes which compressed and deteriorated the macrophages harboring Leishman bodies. The primary mode of action of 6-gingerol and amphotericin B involved broad mechanistic insights providing a coherent basis for further clinical study as a potential drug candidate for CL. In conclusion, 6-gingerol with amphotericin B synergistically exerted anti-leishmanial activity in vitro and in vivo and potentiated macrophages' leishmanicidal activity, modulated Th1- and Th2-related phenotypes improved the histopathological changes in the BALB/c mice infected with L. major. They elevated the leukocyte infiltration into the lesions. Therefore, this combination should be considered for treating volunteer patients with CL in clinical studies.