22 research outputs found
The Role of Epigenetic and Biological Biomarkers in the Diagnosis of Periodontal Disease: A Systematic Review Approach
Control of Klebsiella pneumoniae Infection in Mice by Using Dissolving Microarray Patches Containing Gentamicin
Antibiotic Therapy and the Gut Microbiome:Investigating the Effect of Delivery Route on Gut Pathogens
The contribution of the gut microbiome to human health has long been established, with normal gut microbiota conferring protection against invasive pathogens. Antibiotics can disrupt the microbial balance of the gut, resulting in disease and the development of antimicrobial resistance. The effect of antibiotic administration route on gut dysbiosis remains under-studied to date, with conflicting evidence on the differential effects of oral and parenteral delivery. We have profiled the rat gut microbiome following treatment with commonly prescribed antibiotics (amoxicillin and levofloxacin), via either oral or intravenous administration. Fecal pellets were collected over a 13-day period and bacterial populations were analyzed by 16S rRNA gene sequencing. Significant dysbiosis was observed in all treatment groups, regardless of administration route. More profound dysbiotic effects were observed following amoxicillin treatment than those with levofloxacin, with population richness and diversity significantly reduced, regardless of delivery route. The effect on specific taxonomic groups was assessed, revealing significant disruption following treatment with both antibiotics. Enrichment of a number of groups containing known gut pathogens was observed, in particular, with amoxicillin, such as the family Enterobacteriaceae. Depletion of other commensal groups was also observed. The degree of dysbiosis was significantly reduced toward the end of the sampling period, as bacterial populations began to return to pretreatment composition. Richness and diversity levels appeared to return to pretreatment levels more quickly in intravenous groups, suggesting convenient parenteral delivery systems may have a role to play in reducing longer term gut dysbiosis in the treatment of infection
A novel design process for selection of attributes for inclusion in discrete choice experiments:Case study exploring variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke
On-line structured prioritisation exercise (SPE). Full survey used to collect data. (DOCX 42Â kb
Dissolving microneedles for intradermal vaccination:manufacture, formulation, and stakeholder considerations
Dendritic Cell-Specific Role for Pellino2 as a Mediator of TLR9 Signaling Pathway
Ubiquitination regulates immune signaling, and multiple E3 ubiquitin ligases have been studied in the context of their role in immunity. Despite this progress, the physiological roles of the Pellino E3 ubiquitin ligases, especially Pellino2, in immune regulation remain largely unknown. Accordingly, this study aimed to elucidate the role of Pellino2 in murine dendritic cells (DCs). In this study, we reveal a critical role of Pellino2 in regulation of the proinflammatory response following TLR9 stimulation. Pellino2-deficient murine DCs show impaired secretion of IL-6 and IL-12. Loss of Pellino2 does not affect TLR9-induced activation of NF-κB or MAPKs, pathways that drive expression of IL-6 and IL-12. Furthermore, DCs from Pellino2-deficient mice show impaired production of type I IFN following endosomal TLR9 activation, and it partly mediates a feed-forward loop of IFN-β that promotes IL-12 production in DCs. We also observe that Pellino2 in murine DCs is downregulated following TLR9 stimulation, and its overexpression induces upregulation of both IFN-β and IL-12, demonstrating the sufficiency of Pellino2 in driving these responses. This suggests that Pellino2 is critical for executing TLR9 signaling, with its expression being tightly regulated to prevent excessive inflammatory response. Overall, this study highlights a (to our knowledge) novel role for Pellino2 in regulating DC functions and further supports important roles for Pellino proteins in mediating and controlling immunity
Chrono-tailored drug delivery systems: recent advances and future directions
Circadian rhythms influence a range of biological processes within the body, with the central clock or suprachiasmatic nucleus (SCN) in the brain synchronising peripheral clocks around the body. These clocks are regulated by external cues, the most influential being the light/dark cycle, in order to synchronise with the external day. Chrono-tailored or circadian drug delivery systems (DDS) aim to optimise drug delivery by releasing drugs at specific times of day to align with circadian rhythms within the body. Although this approach is still relatively new, it has the potential to enhance drug efficacy, minimise side effects, and improve patient compliance. Chrono-tailored DDS have been explored and implemented in various conditions, including asthma, hypertension, and cancer. This review aims to introduce the biology of circadian rhythms and provide an overview of the current research on chrono-tailored DDS, with a particular focus on immunological applications and vaccination. Finally, we draw on some of the key challenges which need to be overcome for chrono-tailored DDS before they can be translated to more widespread use in clinical practice.<br/