The potential use of toll-like receptor (TLR) agonists and antagonists as prophylactic and/or therapeutic agents

2009 ◽  
Vol 31 (3) ◽  
pp. 331-338 ◽  
Author(s):  
Amani Makkouk ◽  
Alexander M. Abdelnoor
2015 ◽  
Vol 59 (5) ◽  
pp. 2867-2874 ◽  
Author(s):  
Atteneri López-Arencibia ◽  
Daniel García-Velázquez ◽  
Carmen M. Martín-Navarro ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
...  

ABSTRACTThein vitroactivity of a novel group of compounds, hexaazatrinaphthylene derivatives, against two species ofLeishmaniais described in this study. These compounds showed a significant dose-dependent inhibition effect on the proliferation of the parasites, with 50% inhibitory concentrations (IC50s) ranging from 1.23 to 25.05 μM against the promastigote stage and 0.5 to 0.7 μM against intracellular amastigotes. Also, a cytotoxicity assay was carried out to in order to evaluate the possible toxic effects of these compounds. Moreover, different assays were performed to determine the type of cell death induced after incubation with these compounds. The obtained results highlight the potential use of hexaazatrinaphthylene derivatives againstLeishmaniaspecies, and further studies should be undertaken to establish them as novel leishmanicidal therapeutic agents.


2021 ◽  
Vol 22 (12) ◽  
pp. 6593
Author(s):  
Kenta H.T. Cho ◽  
Mhoyra Fraser ◽  
Bing Xu ◽  
Justin M. Dean ◽  
Alistair J. Gunn ◽  
...  

Background: Toll-like receptor (TLR) agonists are key immunomodulatory factors that can markedly ameliorate or exacerbate hypoxic–ischemic brain injury. We recently demonstrated that central infusion of the TLR7 agonist Gardiquimod (GDQ) following asphyxia was highly neuroprotective after 3 days but not 7 days of recovery. We hypothesize that this apparent transient neuroprotection is associated with modulation of seizure-genic processes and hemodynamic control. Methods: Fetuses received sham asphyxia or asphyxia induced by umbilical cord occlusion (20.9 ± 0.5 min) and were monitored continuously for 7 days. GDQ 3.34 mg or vehicle were infused intracerebroventricularly from 1 to 4 h after asphyxia. Results: GDQ infusion was associated with sustained moderate hypertension that resolved after 72 h recovery. Electrophysiologically, GDQ infusion was associated with reduced number and burden of postasphyxial seizures in the first 18 h of recovery (p < 0.05). Subsequently, GDQ was associated with induction of slow rhythmic epileptiform discharges (EDs) from 72 to 96 h of recovery (p < 0.05 vs asphyxia + vehicle). The total burden of EDs was associated with reduced numbers of neurons in the caudate nucleus (r2 = 0.61, p < 0.05) and CA1/2 hippocampal region (r2 = 0.66, p < 0.05). Conclusion: These data demonstrate that TLR7 activation by GDQ modulated blood pressure and suppressed seizures in the early phase of postasphyxial recovery, with subsequent prolonged induction of epileptiform activity. Speculatively, this may reflect delayed loss of early protection or contribute to differential neuronal survival in subcortical regions.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yann Ehinger ◽  
Ziyang Zhang ◽  
Khanhky Phamluong ◽  
Drishti Soneja ◽  
Kevan M. Shokat ◽  
...  

AbstractAlcohol Use Disorder (AUD) affects a large portion of the population. Unfortunately, efficacious medications to treat the disease are limited. Studies in rodents suggest that mTORC1 plays a crucial role in mechanisms underlying phenotypes such as heavy alcohol intake, habit, and relapse. Thus, mTORC1 inhibitors, which are used in the clinic, are promising therapeutic agents to treat AUD. However, chronic inhibition of mTORC1 in the periphery produces undesirable side effects, which limit their potential use for the treatment of AUD. To overcome these limitations, we designed a binary drug strategy in which male mice were treated with the mTORC1 inhibitor RapaLink-1 together with a small molecule (RapaBlock) to protect mTORC1 activity in the periphery. We show that whereas RapaLink-1 administration blocked mTORC1 activation in the liver, RapaBlock abolished the inhibitory action of Rapalink-1. RapaBlock also prevented the adverse side effects produced by chronic inhibition of mTORC1. Importantly, co-administration of RapaLink-1 and RapaBlock inhibited alcohol-dependent mTORC1 activation in the nucleus accumbens and attenuated alcohol seeking and drinking.


2016 ◽  
Vol 60 (9) ◽  
pp. 5111-5121 ◽  
Author(s):  
Emma Hennessy ◽  
Claire Adams ◽  
F. Jerry Reen ◽  
Fergal O'Gara

ABSTRACTStatins are members of a class of pharmaceutical widely used to reduce high levels of serum cholesterol. In addition, statins have so-called “pleiotropic effects,” which include inflammation reduction, immunomodulation, and antimicrobial effects. An increasing number of studies are emerging which detail the attenuation of bacterial growth andin vitroandin vivovirulence by statin treatment. In this review, we describe the current information available concerning the effects of statins on bacterial infections and provide insight regarding the potential use of these compounds as antimicrobial therapeutic agents.


2015 ◽  
Vol 11 (02) ◽  
pp. 97 ◽  
Author(s):  
Leonidas H Duntas ◽  
Alicja Hubalewska-Dydejczyk ◽  
◽  

The essential trace element selenium (Se) is constitutively incorporated as selenocysteine, in proteins, among others in antioxidative selenoproteins, such as glutathione peroxidase(s) and thioredoxin reductase. Since chronic inflammation is thought to deplete Se stores in the body, Se supplementation should be considered in prolonged inflammatory states, Se being the trace element the most affected in chronic or low-grade inflammation. Se administration might also be beneficial in bacterial and viral diseases as well as metabolic and autoimmune diseases. In order to maintain a Se steady state, or “selenostasis,” Se supplementation, via either diet or compounds, is required to preserve the activity of selenoproteins in antioxidative and redox processes. Importantly, Se could play a pivotal role in the maintenance of homeostasis in infected tissues by inhibiting the proinflammatory toll-like receptor nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway and counteracting proinflammatory cytokine action. Finally, while Se status shows considerable promise as a valid marker of inflammatory and autoimmune disease, new functional Se nanoparticles and highly bioavailable selenomethionine compounds will in all probability provide a more efficacious and reliable intervention tool in both preventive and therapeutic disease management.


2019 ◽  
Vol 10 (12) ◽  
pp. 8208-8217 ◽  
Author(s):  
Jin Zhang ◽  
Heather L. Tyler ◽  
Mona H. Haron ◽  
Colin R. Jackson ◽  
David S. Pasco ◽  
...  

Insoluble beta glucans and TLR agonists derived from colonizing microorganisms are responsible for in vitro macrophage activation by edible mushrooms.


2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.


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