28 research outputs found
Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection
Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model
Chemical profiles and cytotoxic activities of essential oils from six species of Baccharis subgenus Coridifoliae (Asteraceae).
This article augments the current know ledge about the chemical-biological properties of Baccharis subgenus Coridifoliae and discusses the therapeutic potentials of these economically unexploited plants
A Magnetically Responsive Biomaterial System for Flexibly Regulating the Duration Between Pro- and Anti-Inflammatory Cytokine Deliveries
While inflammation can be problematic, it is nonetheless necessary for proper tissue regeneration. However, it remains unclear how the magnitude and duration of the inflammatory response impacts regenerative outcome. This is partially due to the difficulty in temporally regulating macrophage phenotype at wound sites. Here, a magnetically responsive biomaterial system potentially capable of temporally regulating macrophage phenotypes through sequential, onâdemand cytokine deliveries is presented. This material system is designed to (i) rapidly recruit proinflammatory macrophages (M1) through initial cytokine deliveries and (ii) subsequently transition macrophages toward antiâinflammatory phenotypes (M2s) through delayed, magnetically triggered cytokine release. Here, the ability of this system to initially deliver proinflammatory cytokines (i.e., monocyte chemoattractant proteinâ1 and interferon gamma), recruit, and harbor an expanding macrophage population, and delay deliveries of antiâinflammatory cytokines (i.e., ILâ4 and ILâ10) until the application of magnetic fields from simple handâheld magnets is demonstrated. Critically, the timing and rate of these delayed deliveries can be remotely/magnetically controlled. This biomaterial system can provide a powerful tool in (i) understanding the relationship between inflammation and regenerative outcome, (ii) developing optimized cytokine delivery strategies, and (iii) clinically implementing those optimized delivery strategies with the onâdemand versatility needed to alter the course of therapies in real time
Pulsatile Chemotherapeutic Delivery Profiles Using Magnetically Responsive Hydrogels
Pulsatile
chemotherapeutic delivery profiles may provide a number
advantages by maximizing the anticancer toxicity of chemotherapeutics,
reducing off-target side effects, and combating adaptive resistance.
While these temporally dynamic deliveries have shown some promise,
they have yet to be clinically deployed from implantable hydrogels,
whose localized deliveries could further enhance therapeutic outcomes.
Here, several pulsatile chemotherapeutic delivery profiles were tested
on melanoma cell survival in vitro and compared to constant (flatline)
delivery profiles of the same integrated dose. Results indicated that
pulsatile delivery profiles were more efficient at killing melanoma
cells than flatline deliveries. Furthermore, results suggested that
parameters like the duration of drug âonâ periods (pulse
width), delivery rates during those periods (pulse heights), and the
number/frequency of pulses could be used to optimize delivery profiles.
Optimization of pulsatile profiles at tumor sites in vivo would require
hydrogel materials capable of producing a wide variety of pulsatile
profiles (e.g., of different pulse heights, pulse widths, and pulse
numbers). This work goes on to demonstrate that magnetically responsive,
biphasic ferrogels are capable of producing pulsatile mitoxantrone
delivery profiles similar to those tested in vitro. Pulse parameters
such as the timing and rate of delivery during âonâ
periods could be remotely regulated through the use of simple, hand-held
magnets. The timing of pulses was controlled simply by deciding when
and for how long to magnetically stimulate. The rate of release during
pulse âonâ periods was a function of the magnetic stimulation
frequency. These findings add to the growing evidence that pulsatile
chemotherapeutic delivery profiles may be therapeutically beneficial
and suggest that magnetically responsive hydrogels could provide useful
tools for optimizing and clinically deploying pulsatile chemotherapeutic
delivery profiles