Macrophage Polarization Towards M2 Phenotype by Curcuminoids Through NF-κB Pathway Inhibition in Adjuvant-Induced Arthritis.

Macrophage polarization is decisive for homeostasis maintenance and tissue repair. Anti-inflammatory properties of curcumin (CUR) have been demonstrated in several studies. It used in the treatment of bone disorders includingrheumatoid arthritis. The present study aims to explore the potential mechanisms of curcumin on macrophage polarization, expression, activation, and cytokine secretion in adjuvant-induced arthritis as well as its possible role in enhancing the therapeutic action of methotrexate (MTX) together with minimizing MTX initiated side-effects. Rats were divided into eight groups as follows; Control group, MTX group: was weekly injected with MTX, CUR group: was treated with a daily oral dose of curcumin, MTX + CUR group: was treated with both methotrexate and curcumin, Adjuvant arthritis group (AIA): was injected with complete Freund's adjuvant for arthritis induction, AIA/MTX group: arthritic rats treated with methotrexate, AIA/CUR group: arthritic rats treated with curcumin and AIA/MTX + CUR: arthritic rats treated with both methotrexate and curcumin. Paw swelling, haematological analysis, immunological studies, histological observations and quantitative immunohistochemical investigations were performed. The present results showed that treating arthritic rats with curcumin either alone or in combination with methotrexate resulted in amelioration in paws inflammation, growth rate, absolute and relative spleen weights, and haematological analyses. Antinuclear antibodies, IL-1ß, IL-8, IL-10, NF-kB levels, and CD68 + joint expression were also ameliorated. The microscopic examination of joint and spleen showed more improvement as apparently normal tissues in treated groups. It can be concluded that curcumin seems to be most promising in regulating macrophage expression, activation, cytokine secretion, and polarization, thus providing a novel insight in the application of curcumin-based treatments.

Mesenchymal Stem Cells and Myeloid-Derived Suppressor Cells Interplay in Adjuvant-Induced Arthritis Rat Model.

There has not been much researchs on the biological relationship between myeloid-derived suppressor cells (MDSCs) and mesenchymal stem cells (MSCs). The goal of the current work is to examine how these cells cooperate with one another in a rat model of adjuvant-induced arthritis (AIA). Three groups of equal numbers of rats were created; the first group served as the control. Complete Freund's adjuvant (CFA) was injected into the second group to induce AIA. The third group underwent MSCstreatment. Three weeks later, ANA, IL-1ß, IL-4, IL-6, IL-10, TNF-α, IFN-γ, M-CSF, iNOS and Arg-1 were determined using ELISA. Flowcytometric studies for MDSCs using CD11bc + and His48 + antibodies were performed. Current results showed significantly higher levels of WBCs, ANA, IL-1, IL-4, IL-6, IL-10, TNF-α, M-CSF, iNOS and Arg-1 along with a significant rise in MDSCs % in the AIA group compared to the control group. As opposed to AIA animals, MSCs administration resulted in a considerable improvement in cytokine levels, supporting the immunomodulation function of MSCs. Histological examination of the joints in the AIA group revealed articular cartilage degradation as well as infiltration of inflammatory cells and fibroplasia. These several evidences suggested that MDSCs may perform various roles in autoimmunity. Understanding how MDSCs and MSCs contribute to arthritis may help their prospective application in immunotherapy. Therefore, the reciprocal collaboration of MSCs and MDSCs must therefore be the subject of new investigations, which can offer new platforms for the development of more effective and individualized therapies for the treatment of immunological illnesses.

Application of either nano fibrillated cellulose methotrexate or nano silicon dioxide methotrexate composites against renal fibrosis in leukemia rat model.

Cellulose derivatives have got growing interest due to their relative abundance and ability to sustain the release of medicaments. In this study, micro- and nano-fibrillated cellulose were prepared from rice straw and used as drug carriers. Both carriers in addition to another one which is nano silicon dioxide were characterized with various techniques. Methotrexate was chosen to be loaded on nano-fibrillated cellulose and nano silicon dioxide. Both methotrexate carriers were evaluated for their possible protective role against renal fibrosis induced by methotrexate in leukemia rat model. Results of this study exhibited that loading methotrexate on either nano-fibrillated cellulose or nano silicon dioxide seems to have an ameliorative role on renal function tests, inflammatory and fibrotic markers of renal tissues. Moreover, the sustained release of methotrexate for long time period maintained by nano-fibrillated cellulose carrier gives it more priority than nano silicon dioxide to be used as an effective novel drug carrier in further medical applications with minimal side effects on kidney tissue in leukemia model.

Sugarcane bagasse lignin, and silica gel and magneto-silica as drug vehicles for development of innocuous methotrexate drug against rheumatoid arthritis disease in albino rats.

The present study clarifies co-therapy action of deliveries from their textural changes point of view. Methotrexate (MTX) was immobilized onto biodegradable lignin, silica gel and iron/silica nanocomposite. Loaded-MTX was i.p. injected into albino rats at doses of 0.25 and 0.5mg/kg/week for 2.5months, after which spleen, liver, testes and knee joint tissues were collected for tests. IFN-γ and IL-17A mRNA gene expressions in spleen in all biological samples were determined by RT-PCR. Physicochemical features of drug carriers were monitored by XRD, BET-PSD, SEM and TEM. Drug inflammatory-site targeting was found to be closely related to the physico-features of deliverers. The interlayered lignin of micro- and meso-pore channels directed MTX toward concealed infected cells in liver and testes tissues, while meso-structured silica flacks satisfied by gathering MTX around knee joints. The magneto-silica nanocomposite targeted MTX toward spleen tissue, which is considered as a lively factory for the production of electron rich compounds.