ABSTRACT
Rheumatoid arthritis is a disabling autoimmune disease with a high global prevalence. Treatment with disease-modifying anti-arthritic drugs (DIMARDs) has been routinely used with beneficial effects but with adverse long-term consequences; novel targeted biologics and small-molecule inhibitors are promising options. In this study, we investigated whether purified omega unsaturated fatty acids (ω-UFAs) and dialysable leukocyte extracts (DLEs) prevented the development of arthritis in a model of collagen-induced arthritis (CIA) in mice. We also investigated whether the transcription factor NF-κB and the NLRP3 inflammasome were involved in the process and whether their activity was modulated by treatment. The development of arthritis was evaluated for 84 days following treatment with nothing, dexamethasone, DLEs, docosahexaenoic acid, arachidonic acid, and oleic acid. Progression of CIA was monitored by evaluating clinical manifestations, inflammatory changes, and histological alterations in the pads' articular tissues. Both DLEs and ω-UFAs led to an almost complete inhibition of the inflammatory histopathology of CIA and this was concomitant with the inhibition of NF-kB and the inhibition of the activation of NLRP3. These data suggest that ω-UFAs and DLEs might have NF-κB as a common target and that they might be used as ancillary medicines in the treatment of arthritis.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antirheumatic Agents/pharmacology , Arthritis, Experimental/prevention & control , Cartilage, Articular/drug effects , Cell Extracts/pharmacology , Fatty Acids, Unsaturated/pharmacology , Leukocytes , Animals , Arachidonic Acid/pharmacology , Arthritis, Experimental/chemically induced , Arthritis, Experimental/metabolism , Arthritis, Experimental/pathology , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Collagen Type II , Dialysis , Docosahexaenoic Acids/pharmacology , Female , Inflammasomes/drug effects , Inflammasomes/metabolism , Mice, Inbred BALB C , Mice, Inbred DBA , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Oleic Acid/pharmacologyABSTRACT
BACKGROUND: Procedures to remove adiposities and skin, such as dermolipectomy, can develop wounds that are difficult to heal by conventional therapies. Mesenchymal stem cells are indicated as potential candidates for regenerative therapy in wounds, due to their multipotentiality, low immunogenicity, modulating capacity of inflammation and tissue modeling processes. CASE REPORT: Patient with dehiscent chronic ulcer secondary to dermolipectomy, who received cutaneous treatment with mesenchymal stem cells. The therapy induced scar formation and neovascularization, as well as the decrease of infiltrated leukocytes and proinflammatory cytokines. Mesenchymal cells are proposed as an interesting alternative for the treatment of postoperative lesions.
INTRODUCCIÓN: Los procedimientos para retirar adiposidades y piel, como la dermolipectomía, pueden desarrollar heridas difíciles de sanar mediante tratamientos convencionales. Se ha señalado que es posible utilizar las células madre mesenquimales en el tratamiento regenerativo en heridas, en virtud de su multipotencialidad, baja inmunogenicidad, capacidad moduladora de inflamación y procesos modeladores de tejidos. CASO CLÍNICO: Paciente con dehiscencia en úlcera crónica secundaria a dermolipectomía, sometida a tratamiento cutáneo con células madre mesenquimales. Se indujo formación de cicatriz y neovascularización, así como la disminución de leucocitos infiltrados y citocinas proinflamatorias. Se propone a las células mesenquimales como una alternativa interesante para el tratamiento de lesiones postoperatorias.
Subject(s)
Body Contouring/adverse effects , Lipectomy/adverse effects , Mesenchymal Stem Cell Transplantation , Regenerative Medicine/methods , Skin Ulcer/therapy , Surgical Wound Dehiscence/therapy , Wharton Jelly/cytology , Adipogenesis , Adult , Antigens, Surface/biosynthesis , Antigens, Surface/genetics , Cell Separation , Chronic Disease , Cicatrix/etiology , Female , Gene Expression , Humans , Inflammation , Mesenchymal Stem Cells , Neovascularization, Physiologic , Osteogenesis , Skin Ulcer/etiology , Surgical Wound Dehiscence/etiology , Wound HealingABSTRACT
Despite the success for the treatment of melanoma such as targeted molecular therapy, the use of such treatments are expensive For this reason, this study was carried out to explore the anti-cancer properties of available drugs that are able to modify the melanoma prognosis. The study was conducted in two phases: Evaluation of pharmacological effects of pentoxifylline (PTX) administered above (60â¯mg/kg) which is the therapeutic dose that is aimed at reducing the side-effect of radiotherapy, and of α- galactosylceramide (GalCer) administered at 100⯵g/kg, as well as their combination using a murine model (BDF1 mice) of melanoma cell line (B16-F1, ATCC). For the radiotherapy phase, 9â¯Gy was applied in the tumor area, before (3 days), during (30â¯min) and after (3 days) the PTXâ¯+â¯GalCer treatment. In both study phases, the mitosis rate, leukocyte infiltration and necro-apoptosis were assessed using histological and immunohistochemical approach and tumor volume evaluation as biomarkers. All treatments showed good prognosis results estimated as reduction of mitosis rate (PTXâ¯+â¯GalCer after radiotherapy and GalCer), increased leukocyte infiltrate (PTXâ¯+â¯GalCer after radiotherapy and GalCer) and necro-apoptosis augmentation (PTXâ¯+â¯GalCer after radiotherapy and radiotherapy control). Nevertheless, a lower development of tumor volume was found in GalCer treatment. In this way, it is possible to suggest that the integrated treatment with immuno-stimulators such as GalCer, plus drug used for peripheral vascular disease (PTX) after radiotherapy is probably an alternative for controlling aggressive melanoma in murine model.
