Anti-proliferative effect of Rosmarinus officinalis L. extract on human melanoma A375 cells

Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed

IgG Response to Intracerebral Xenotransplantation: Specificity and Role in the Rejection of Porcine Neurons

International audienceXenogenic fetal neuroblasts are considered as a potential source of transplantable cells for the treatment of neurodegenerative diseases, but immunological barriers limit their use in the clinic. While considerable work has been performed to decipher the role of the cellular immune response in the rejection of intracerebral xenotransplants, there is much still to learn about the humoral reaction. To this end, the IgG response to the transplantation of fetal porcine neural cells (PNC) into the rat brain was analyzed. Rat sera did not contain preformed antibodies against PNC, but elicited anti-porcine IgG was clearly detected in the host blood once the graft was rejected. Only the IgG1 and IgG2a subclasses were up-regulated, suggesting a T-helper 2 immune response. The main target of these elicited IgG antibodies was porcine neurons, as determined by double labeling in vitro and in vivo. Complement and antiporcine IgG were present in the rejecting grafts, suggesting an active role of the host humoral response in graft rejection. This hypothesis was confirmed by the prolonged survival of fetal porcine neurons in the striatum of immunoglobulin-deficient rats. These data suggest that the prolonged survival of intracerebral xenotransplants relies on the control of both cell-mediated and humoral immune responses

Supplemental Figures S1-S8: Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci

Supplemental Figures and Table S1-S8 for "Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci" H-00088-2019, to the American Journal of Physiology-Heart and Circulatory Physiology

Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci

Supplemental Figures and Table S1-S8 for "Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci" H-00088-2019, to the American Journal of Physiology-Heart and Circulatory Physiology

Generation of Rag1 and Il2rg immunodeficient rats and application to humanization studies

International audienceModeling the immune response and rational immune approaches in vivo have relied heavily on studies performed in immunodeficient mouse models. These mouse models are groundbreaking platforms to humanize different tissues and organs and to evaluate compounds to treat a variety of human diseases, from cancer and infectious diseases to allergies, inflammation and GVHD. Rats are ideally suited to perform experiments in which larger size is needed and are still a small animal model suitable for rodent facilities.We describe here the generation of Il2rg-deficient rats and their crossing with previously described Rag1-deficient rats, generating for the first time double-mutant Rat Rag1 and Il2rG KO (RRG) animals