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showing 10 items of 12132 documents
Danger signals: Chemotherapy enhancers?
2017
IF 9.614; International audience; Endogenous danger signals are molecules normally present in a given cell compartment that are rapidly released following cell stress and induce immune responses. We and others have shown that dying tumor cells treated with some chemotherapies are able to induce anticancer immune responses, which rely on their release of danger signals such as the nuclear protein HMGB1. DNA can also be released from chemotherapy-treated tumor cells, act as a danger signal, and boost anticancer immunity. While the immunostimulatory properties of DNA have been identified for decades, the recent discovery of a novel family of receptors, cytosolic DNA sensors, has provided a nov…
Antagonization of IL-17A Attenuates Skin Inflammation and Vascular Dysfunction in Mouse Models of Psoriasis
2019
Besides skin inflammation, patients with severe psoriasis suffer from an increased risk of cardiovascular mortality. IL-17A plays a central role in the development of psoriasis and might connect skin and vascular disease. The aim of this study was to clarify whether anti-IL-17A therapy could also ameliorate the vascular dysfunction associated with severe psoriasis. We analyzed three murine models with varying severities of psoriasis-like skin disease concerning their vascular function and inflammation: (i) K14-IL-17A(ind/+) mice with keratinocyte-specific IL-17A overexpression and an early-onset severe psoriasis-like phenotype; (ii) homozygous CD11c-IL-17A(ind/ind) and heterozygous CD11c-IL…
2018
The catabolic process of autophagy plays important functions in inflammatory and immune responses by modulating innate immunity and adaptive immunity. Over the last decade, a cell-intrinsic role for autophagy in modulating CD4 T cell functions and differentiation was revealed. After the initial observation of autophagosomes in effector CD4 T cells, further work has shown that not only autophagy levels are modulated in CD4 T cells in response to environmental signals but also that autophagy critically affects the biology of these cells. Mouse models of autophagy deletion in CD4 T cells have indeed shown that autophagy is essential for CD4 T cell survival and homeostasis in peripheral lymphoi…
Interleukin-2 Functionalized Nanocapsules for T Cell-Based Immunotherapy.
2016
A major demand on immunotherapy is the direct interference with specific immune cells in vivo. In contrast to antibody-engineered nanoparticles to control dendritic cells function, targeting of T cells for biomedical applications still remains an obstacle as they disclose reduced endocytic activities. Here, by coupling the cytokine interleukin-2 (IL-2) to the surface of hydroxyethyl starch nanocapsules, we demonstrated a direct and specifc T cell targeting in vitro and in vivo by IL-2 receptor-mediated internalization. For this purpose, defined amounts of azide-functionalized IL-2 were linked to alkyne-functionalized hydroxyethyl starch nanocapsules via copper-free click reactions. In combi…
Targeted Activation of T Cells with IL-2-Coupled Nanoparticles
2020
Interleukin-2 (IL-2) is a T cell growth factor particularly required in regulatory T cell maintenance and memory T cell responses. High-dose IL-2 treatment was the first FDA-approved immunotherapy for cancer, while low-dose IL-2 administration has shown promise in allograft rejection and autoimmune and inflammatory diseases. However, its pleiotropic nature and the existence of IL-2 receptors with different binding affinity limit its therapeutic application. For an improved clinical applicability of the cytokine, a targeted receptor assignment must, therefore, be achieved. Nanoparticles allow controlling the location and dose of immunomodulating compounds and to specifically address specific…
The cyto-protective effects of LH on ovarian reserve and female fertility during exposure to gonadotoxic alkylating agents in an adult mouse model.
2021
Abstract STUDY QUESTION Does LH protect mouse oocytes and female fertility from alkylating chemotherapy? SUMMARY ANSWER LH treatment before and during chemotherapy prevents detrimental effects on follicles and reproductive lifespan. WHAT IS KNOWN ALREADY Chemotherapies can damage the ovary, resulting in premature ovarian failure and reduced fertility in cancer survivors. LH was recently suggested to protect prepubertal mouse follicles from chemotoxic effects of cisplatin treatment. STUDY DESIGN, SIZE, DURATION This experimental study investigated LH effects on primordial follicles exposed to chemotherapy. Seven-week-old CD-1 female mice were randomly allocated to four experimental groups: C…
A selective inhibitor of the Polo-box domain of Polo-like kinase 1 identified by virtual screening
2018
Graphical abstract
Risk factors for anthroponotic cutaneous leishmaniasis in unresponsive and responsive patients in a major focus, southeast of Iran
2018
Cutaneous leishmaniasis (CL) is a serious health challenge at the global level due to Leishmania tropica. This study was conducted to evaluate the risk factors associated with anthroponotic CL (ACL) in unresponsive (patient who does not heal and remains with an active lesion, despite receiving two courses of intra-lesional Glucantime along with cryotherapy and one cycle of systemic Glucantime) and responsive patients in a major focus in southeastern Iran. A case-control study was conducted from April 2015 to October 2016 in the southeast of Iran. Patients were recruited in a major ACL focus from unresponsive and responsive cases. These patients were compared for environmental, clinical, and…
Good's syndrome and recurrent leishmaniasis: A case report and review of literature
2020
We report the case of a 56-year-old Caucasian male affected by thymoma and myasthenia gravis that developed recurrent visceral leishmaniasis 11 years after thymectomy. After treatment of each relapse with liposomal amphotericin B the PCR-Leishmania was negative and the patient showed clinical improvement. An immunologic work-up was performed showing lymphopenia with an important decrease in CD4+ T cells (52 cells/μ) and CD4/CD8 ratio (0.2). HIV test was negative. On the basis of previous thymoma and myasthenia gravis and on the basis of the immunological profile a diagnosis of Good's syndrome was made. Since IFNγ plays a main role in the control of Leishmania infection the production of IFN…
Medicinal Plants and Natural Products as Potential Sources for Antiparkinson Drugs
2016
Parkinsonʼs disease is a progressive neurodegenerative dysfunction characterized by the loss of pigmented dopaminergic neurons of the nigrostriatal system with a consequent dopamine decrease. The reduction of dopamine levels produces neuronal damage, depigmentation of the substantia nigra, and the presence of intracellular inclusions in dopaminergic neurons. Treatments for Parkinsonʼs disease aim for improving these motor symptoms by increasing the dopaminergic signal in the striatum with levodopa in combination with enzyme inhibitors or anticholinergic drugs. Nevertheless, natural products can act as neuroprotective agents by reducing the progression of the disease and the inflammatory pro…