Potent immunosuppressive activity of a phosphodiesterase-4 inhibitor N-acylhydrazone in models of lipopolysaccharide-induced shock and delayed-type hypersensitivity reaction. | LitMetric
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), CEP 40296-710 Salvador, BA, Brazil; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, CEP 41253-190 Salvador, BA, Brazil. Electronic address:
Published: December 2018
AI Article Synopsis
Article Abstract
Immunosuppressive drugs are widely used for the treatment of immune-mediated diseases and inflammation, but the toxicity and side effects of the available immunosuppressors make the search of new agents of great relevance. Here, we evaluated the immunomodulatory activity of an N-acylhydrazone derivative, (E)-N'-(3,4-dimethoxybenzylidene)-4-methoxybenzohydrazide (LASSBio-1386), a phosphodiesterase-4 (PDE-4) inhibitor. LASSBio-1386 inhibited lymphocyte activation in a concentration-dependent fashion, decreasing lymphoproliferation and IFN-γ and IL-2 production stimulated by anti-CD3/CD28 mAbs or concanavalin A (Con A) and inducing cell-cycle arrest in the G0/G1 phase. These effects were not blocked by RU486, a glucocorticoid receptor (GR) antagonist, indicating an effect independent of glucocorticoid receptor activation. Combination index-isobologram analysis indicates a synergistic effect between LASSBio-1386 and dexamethasone in lymphoproliferation inhibition. LASSBio-1386 presented immunomodulatory action in macrophage cultures, as observed by a significant and concentration-dependent decrease in NO and TNF-α production, an effect achieved by reducing IĸB expression and NF-κB activation. In the mouse model of endotoxic shock, LASSBio-1386 at 50 and 100 mg/kg protected 50 and 85% of mice against LPS-induced lethality, respectively. In agreement to its in vitro action, treatment with 100 mg/kg of LASSBio-1386 reduced TNF-α and IL-1β serum levels, while increased IL-6 and IL-10. Finally, LASSBio-1386 reduced the paw edema in a BSA-induced delayed-type hypersensitivity model. These findings demonstrate the immunomodulatory and immunosuppressant effects of LASSBio-1386 and indicate this molecule is a promising pharmacologic agent for immune-mediated diseases.
Tattooing has become a popular global trend in industrialised countries, with the highest prevalence rates of up to 30-40 % in the adult population younger than 40 years. Common tattoo inks may contain heavy metals, polycyclic aromatic hydrocarbons, and primary aromatic amines, toxic if exceeding permissible limits. It is estimated that about 14.
Background: While many studies have reported renal involvement in sarcoidosis, there is limited description of the pathological manifestations of renal sarcoidosis (RS). This study aimed to explore the standardized pathological diagnosis of RS while evaluating the relationship among pathology, clinical manifestations, and prognosis.
Methods: We conducted a retrospective, single-center study of RS in renal biopsy cases treated in our department between January 2019 and December 2023.
Department of Cardiovascular Surgery, Fukushima Dai-Ichi Hospital, Fukushima, Japan; Japanese Regulatory Committee for Endovascular Treatment of Varicose Veins.
Objective: Cyanoacrylate closure (CAC) is a minimally invasive technique for treating axial venous reflux. However, the incidence of serious adverse events (AEs) related to CAC is concerning. With an increasing number of patients receiving CAC and insufficient safety data in Japan, this study aimed to investigate the safety profile of CAC, focusing on the types and incidence of AEs.
New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells. Deficiency or alterations of synaptic input and neurotrophic factors result in trans-neuronal degeneration of the inner retinal cells. Thus, the disruption of photoreceptors takes place.
