Bone marrow mesenchymal stem cells to ameliorate experimental autoimmune encephalomyelitis via modifying expression patterns of miRNAs.

INTRODUCTION: Clinical and experimental studies highlighted the significant therapeutic role of Mesenchymal stem cells (MSCs) in neurodegenerative diseases. MSCs possess potent immunomodulatory properties by releasing exosomes, which generate a suitable microenvironment. microRNAs (miRNAs), as one of several effective bioactive molecules of exosomes, influence cellular communication and activities in recipient cells. Recent studies revealed that miRNAs could control the progression of multiple sclerosis (MS) via differentiation and function of T helper cells (Th). METHODS: Here, we investigated the therapeutic effects of syngeneic-derived BM-MSC in experimental autoimmune encephalomyelitis (EAE) mouse model of MS by evaluating expression profile of miRNAs, pro- and anti-inflammatory in serum and brain tissues. Three-time scheme groups (6th day, 6th & 12th days, and 12th day, of post-EAE induction) were applied to determine the therapeutic effects of intraperitoneally received 1*106 of BM-MSCs. RESULTS: The expression levels of mature isoforms of miR-193, miR-146a, miR-155, miR-21, and miR-326 showed that BM-MSCs treatment attenuated the EAE clinical score and reduced clinical inflammation as well as demyelination. The improved neurological functional outcome associated with enhanced expression of miR-193 and miR-146a, but decreased expression levels of miR-155, miR-21, and miR-326 were followed by suppressing effects on Th1/Th17 immune responses (reduced levels of IFN-γand IL-17 cytokine expression) and induction of Treg cells, immunoregulatory responses (increase of IL-10, TGF-ß, and IL-4) in treatment groups. CONCLUSION: Our findings suggest that BM-MSCs administration might change expression patterns of miRNAs and downstream interactions followed by immune system modulation. However, there is a need to carry out future human clinical trials and complementary experiments.

Curcumin's spice-infused therapeutic promise: disease severity alleviation in a mouse model of multiple sclerosis via modulation of immune responses.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune central nervous system (CNS) disorder indicated by demyelination, chronic inflammation, and neuronal destruction. Regional demyelination, inflammation responses, scar development, and various axonal damage are pathological characteristics of MS. Curcumin is a hydrophobic polyphenol extracted from the rhizome of the turmeric plant. In addition to anti-inflammatory effects, beneficial therapeutic effects such as antioxidant, anti-cancer and nerve protection have also been seen from this compound. The purpose of the current investigation was to provide light on the potential benefits of Curcumin in treating experimental autoimmune encephalomyelitis (EAE), the animal model of MS. METHODS AND RESULTS: in Female C57BL/6 mice were used to induce EAE through myelin oligodendroglial glycoprotein (MOG). Curcumin doses of 100 and 200 mg/kg were administered orally in the treatment groups starting on the first day of EAE induction. Brains and splenocytes were extracted from euthanized animals on day 25 following EAE induction. Demyelination and leukocyte infiltration, proliferation, cytokine, and gene expression profiles were assessed. Our findings demonstrate that both low and high doses of Curcumin decreased the progression of EAE. Histological analyses revealed low infiltration of leukocytes into the CNS. Curcumin therapy enhanced Th2 and Treg cell secretion of IL-4, IL-10, and TGF-ß although considerably decreasing IFN-γ and TNF-α. Curcumin-induced Th2 and Treg cell cytokine production and transcription factor gene expression (IL-13, GATA3, STAT6 and IL-35, CTLA4, Foxp3) and anti-inflammatory cytokines (IL-27, IL-33). CONCLUSION: Overall, these findings provide additional evidence that Curcumin can slow disease development and alleviate symptoms in EAE through stimulating Treg and Th2 cell polarization. They support Curcumin's potential therapeutic role in MS.

Niosomes nanoparticles as a novel approach in drug delivery enhances anticancer properties of chrysin in human ovarian carcinoma cells (SKOV3): an in vitro study.

Chrysin (Chr) has drawn a lot of attention recently due to its possible anticancer properties. However, Chr's short half-life and low bioavailability restricted its utility as a medicinal agent. The purpose of this research is to design, synthesize, and test the cytotoxic effects of nano-niosomes containing chrysin (Chr-Nio) on the SKOV3 ovarian cancer cell line. Chr-Nio has a nanoparticle polydispersity index (PDI) of 0.156 and a zeta potential of - 27.4 mV, with an average diameter of 105 nm. Furthermore, Chr was encapsulated in Nio with an entrapment effectiveness of 85.5%. Chr-Nio cytotoxicity was shown to be more than free Chr in a time- and dose-dependent manner. Furthermore, as compared to free Chr-treated cells, the mRNA expression level of apoptotic genes Bcl-2, Bax, and caspase-3 in Chr-Nio-treated cells was considerably altered. According to the data, Chr may inhibit SKOV3 cell migration in vitro scratch wound experiments in a dose-dependent manner, and cells treated with Chr-Nio had the highest percentage of cell death. The findings of this study suggested that encapsulating Chr in niosome nanoparticles might be an effective medication delivery strategy for increasing Chr anticancer effects in the treatment of ovarian cancer.

Oral Administration of Myelin Oligodendrocyte Glycoprotein Attenuates Experimental Autoimmune Encephalomyelitis through Induction of Th2/Treg Cells and Suppression of Th1/Th17 Immune Responses.

Multiple Sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral administration of a Myelin Oligodendrocyte Glycoprotein (MOG) in the treatment of EAE. Female C57BL/6 mice were utilized in three groups (Control group, received PBS orally; prevention group, oral administration of MOG35-55 two weeks before EAE induction; treatment group, oral administration of MOG35-55 after EAE induction). MOG administration, both as prevention and treatment, significantly controlled clinical score, weight loss, CNS inflammation, and demyelination, mainly through the modulation of T cell proliferation, and reduction in pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-γ, IL-17, T-bet, and ROR-γt. MOG administration, both as prevention and treatment, also induced anti-inflammatory cytokines and transcription factors, including IL-4, TGF-ß, GATA-3, and Foxp3. The results showed that oral administration of MOG, both as prevention and treatment, could efficiently control EAE development. Immunomodulatory mechanisms include the induction of Th2 and Treg cells and the suppression of pro-inflammatory Th1 and Th17 cells.

Development, Characterization, and In Vitro Evaluation of Cytotoxic Activity of Rutin Loaded PCL-PEG Nanoparticles Against Skov3 Ovarian Cancer Cell.

BACKGROUND AND PURPOSE: Rutin (RUT) is one of the phenolic compounds found in the invasive plant species, Carpobrotus edulis. Several studies have confirmed numerous pharmacological properties of RUT, including antioxidant, antidiabetic, anti-inflammatory, antimicrobial and anticancer activities. As a result, the goal of this work was to make RUT-loaded PCL-PEG and test its anti-cancer effects against the Skov3 human ovarian cancer cell line. MATERIALS AND METHODS: The NPs were made using the W1/O/W2 process, and their physicochemical properties were assessed by FE-SEM, FTIR, and DLS. MTT assay were used to investigate the anti-proliferative characteristics of drug-loaded NPs. Real-time PCR was also utilized to  examine the expression levels of apoptotic genes including caspase-8, -9, -3, and Bax, as well as anti-apoptotic genes like Bcl-2. RESULTS: Cytotoxicity testing revealed that RUT-loaded PCL-PEG improved cytotoxicity in a dose- and time-dependent manner. In treated MDA-MB-231 cells with RUT-loaded PCL-PEG, there was a significant up-regulation of caspase-8, -9, -3, and Bax genes compared to treated cells with free RUT. CONCLUSION: Finally, RUT-loaded PCL-PEG NPs are recommended as ideal delivery nanocarriers for enhancing RUT's anticancer characteristics for ovarian cancer treatment.