Search results for "Modula"
showing 10 items of 1481 documents
1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro.
2017
We have previously demonstrated the nucleic acid binding capacity of phenanthridine derivatives (PHTs). Because nucleic acids are potent inducers of innate immune response through Toll-like receptors (TLRs), and because PTHs bear a structural resemblance to commonly used synthetic ligands for TLR7/8, we hypothesized that PHTs could modulate/activate immune response. We found that compound M199 induces secretion of IL-6, IL-8 and TNFα in human PBMCs and inhibits TLR3/9 activation in different cellular systems (PBMCs, HEK293 and THP-1 cell lines).
Plant polyphenols, chemoreception, taste receptors and taste management
2019
International audience; Purpose of review Polyphenols display beneficial health effects through chemopreventive actions on numerous chronic diseases including cancers, metabolic disorders, reproductive disorders and eating behaviour disorders. According to the principle of chemoreception, polyphenols bind cellular targets capable of accepting their stereochemistry, namely metabolizing enzymes and protein receptors, including taste receptors. The extraoral expression of taste receptors and their pharmacological interest in terms of novel drug therapies open up new perspectives on the potential use of these compounds and their interactions with other chemicals in cells. These new perspectives…
Dendritic cells tip the balance towards induction of regulatory T cells upon priming in experimental autoimmune encephalomyelitis
2016
Counter-balancing regulatory mechanisms, such as the induction of regulatory T cells (Treg), limit the effects of autoimmune attack in neuroinflammation. However, the role of dendritic cells (DCs) as the most powerful antigen-presenting cells, which are intriguing therapeutic targets in this context, is not fully understood. Here, we demonstrate that conditional ablation of DCs during the priming phase of myelin-specific T cells in experimental autoimmune encephalomyelitis (EAE) selectively aborts inducible Treg (iTreg) induction, whereas generation of T helper (Th)1/17 cells is unaltered. DCs facilitate iTreg induction by creating a milieu with high levels of interleukin (IL)-2 due to a st…
ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker.
2019
Abstract Alzheimer’s disease (AD) represents a global burden in the economics of healthcare systems. Amyloid-β (Aβ) peptides are formed by amyloid-β precursor protein (AβPP) cleavage, which can be processed by two pathways. The cleavage by the α-secretase A Disintegrin And Metalloprotease 10 (ADAM10) releases the soluble portion (sAβPPα) and prevents senile plaques. This pathway remains largely unknown and ignored, mainly regarding pharmacological approaches that may act via different signaling cascades and thus stimulate non-amyloidogenic cleavage through ADAM10. This review emphasizes the effects of natural compounds on ADAM10 modulation, which eventuates in a neuroprotective mechanism. M…
Harnessing the potential of noninvasive in vivo preclinical imaging of the immune system: challenges and prospects.
2016
Preclinical imaging has become a powerful method for investigation of in vivo processes such as pharmacokinetics of therapeutic substances and visualization of physiologic and pathophysiological mechanisms. These are important aspects to understand diseases and develop strategies to modify their progression with pharmacologic interventions. One promising intervention is the application of specifically tailored nanoscale particles that modulate the immune system to generate a tumor targeting immune response. In this complex interaction between immunomodulatory therapies, the immune system and malignant disease, imaging methods are expected to play a key role on the way to generate new thera…
Structure-Activity Relationships of Cytotoxic Lactones as Inhibitors and Mechanisms of Action.
2020
Background: Some lactones prevent protein Myb-dependent gene expression. Objective: The object is to calculate inhibitors of Myb-brought genetic manifestation. Methods: Linear quantitative structure–potency relations result expanded, among sesquiterpene lactones of a variety of macrocycles (pseudoguaianolides, guaianolides, eudesmanolides and germacranolides), to establish which part of the molecule constitutes their pharmacophore, and predict their inhibitory potency on Myb-reliant genetic manifestation, which may result helpful as leads for antileukaemic therapies with a new mechanism of action. Results: Several count indices are connected with structure–activity. The α-methylene-γ-lacto…
Disconnecting bones within the jaw-otic network modules underlies mammalian middle ear evolution
2019
The origin of the mammalian middle ear ossicles from the craniomandibular articulation of their synapsid ancestors is a key event in the evolution of vertebrates. The richness of the fossil record and the multitude of developmental studies have provided a stepwise reconstruction of this evolutionary innovation, highlighting the homology between the quadrate, articular, pre-articular and angular bones of early synapsids with the incus, malleus, gonial and ectotympanic bones of derived mammals, respectively. There are several aspects involved in this functional exaptation: (i) an increase of the masticatory musculature; (ii) the separation of the quadrate bone from the cranium; and (iii) the …
Immunomodulatory activity of Humulus lupulus bitter acids fraction: Enhancement of natural killer cells function by NKp44 activating receptor stimula…
2019
Abstract Humulus lupulus (Hop) contains numerous metabolites with anticancer potential. Despite this, their immunomodulatory activity, and in particular of bitter acids, is unknown. In this study, we demonstrated that a Hop pellet extract fraction containing bitter acids possesses immunomodulatory activity by enhancing Natural Killer (NK) cells function. After fractionation by semi-preparative Liquid Chromatography, three different fractions were obtained. The phytocomplex and the fractions were tested to verify the ability to modulate the NK compartment. Cytofluorimetric analysis revealed that a fraction containing bitter acids was able to up-regulate of NKG2D and NKp44 activating receptor…
Rheostatic Functions of Mast Cells in the Control of Innate and Adaptive Immune Responses
2017
Mast cells are evolutionarily ancient cells, endowed with a unique developmental, phenotypic, and functional plasticity. They are resident cells that participate in tissue homeostasis by constantly sampling the microenvironment. As a result of their large repertoire of receptors, they can respond to multiple stimuli and selectively release different types and amounts of mediator. Here, we present and discuss the recent mast cell literature, focusing on studies that demonstrate that mast cells are more than a switch that is turned âoffâ when in the resting state and âonâ when in the degranulating state. We propose a new vision of mast cells in which, by operating in a ârheostaticâ…
Regulatory T cells and vaccine effectiveness in older adults. Challenges and prospects
2021
Since the discovery of lymphocytes with immunosuppressive activity, increasing interest has arisen in their possible influence on the immune response induced by vaccines. Regulatory T cells (Tregs) are essential for maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. However, they also limit beneficial immune responses by suppressing anti-infectious and anti-tumor immunity. Mounting evidence suggests that Tregs are involved, at least in part, in the low effectiveness of immunization against various diseases where it has been difficult to obtain protective vaccines. Interestingly, increased activity of Tregs is associated with aging, …