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| 2. |
- Reis, Edimara S., et al.
(författare)
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Safety profile after prolonged C3 inhibition
- 2018
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 197, s. 96-106
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Tidskriftsartikel (refereegranskat)abstract
- The central component of the complement cascade, C3, is involved in various biological functions, including opsonization of foreign bodies, clearance of waste material, activation of immune cells, and triggering of pathways controlling development. Given its broad role in immune responses, particularly in phagocytosis and the clearance of microbes, a deficiency in complement C3 in humans is often associated with multiple bacterial infections. Interestingly, an increased susceptibility to infections appears to occur mainly in the first two years of life and then wanes throughout adulthood. In view of the well-established connection between C3 deficiency and infections, therapeutic inhibition of complement at the level of C3 is often considered with caution or disregarded. We therefore set out to investigate the immune and biochemical profile of non-human primates under prolonged treatment with the C3 inhibitor compstatin (Cp40 analog). Cynomolgus monkeys were dosed subcutaneously with Cp40, resulting in systemic inhibition of C3, for 1 week, 2 weeks, or 3 months. Plasma concentrations of both C3 and Cp40 were measured periodically and complete saturation of plasma C3 was confirmed. No differences in hematological, biochemical, or immunological parameters were identified in the blood or tissues of animals treated with Cp40 when compared to those injected with vehicle alone. Further, skin wounds showed no signs of infection in those treated with Cp40. In fact, Cp40 treatment was associated with a trend toward accelerated wound healing when compared with the control group. In addition, a biodistribution study in a rhesus monkey indicated that the distribution of Cp40 in the body is associated with the presence of C3, concentrating in organs that accumulate blood and produce C3. Overall, our data suggest that systemic C3 inhibition in healthy adult non-human primates is not associated with a weakened immune system or susceptibility to infections.
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| 3. |
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| 4. |
- Belibasakis, GN, et al.
(författare)
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Advances in Oral Mucosal Immunity and the Microbiome
- 2019
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Ingår i: Advances in experimental medicine and biology. - Cham : Springer International Publishing. - 0065-2598. ; 1197, s. 1-9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Belibasakis, GN, et al.
(författare)
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Frontiers in Oral Mucosal Immunity and the Microbiome
- 2021
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Ingår i: Frontiers in oral health. - : Frontiers Media SA. - 2673-4842. ; 2, s. 821148-
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Tidskriftsartikel (refereegranskat)abstract
- The 2nd International Conference on Oral Mucosal Immunity and the Microbiome (OMIM) took place at the Grecotel Kos Imperial Hotel, Kos, Greece, between 25th and 30th September 2021, under the auspices of the Aegean Conferences. This has only been the second Aegean Conference of this thematic, the first one having taken place in 2018 in Crete, during the same period of the year. Given the hardships in travel and heightened infection transmission risks amid the COVID-19 pandemic, the Conference was well attended by 29 international speakers across the world. For many of the participants, this was the first conference travel in the post-pandemic era, and quite significant that it has taken place on the island of Hippocrates. Stringent regional health and safety regulations had to be followed to accomplish for this in-person Conference to take place. Frontiers in Oral Health has hosted papers from presentations of the Conference, whereas the present article serves as the proceedings of the Conference with summaries of the presentations.
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| 6. |
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| 7. |
- Belibasakis, GN, et al.
(författare)
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Preface
- 2019
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Ingår i: ORAL MUCOSAL IMMUNITY AND MICROBIOME. - 0065-2598. ; 1197, s. V-V
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
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| 9. |
- Bostanci, N, et al.
(författare)
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TREM-1 Is Upregulated in Experimental Periodontitis, and Its Blockade Inhibits IL-17A and RANKL Expression and Suppresses Bone loss
- 2019
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a modifier of local and systemic inflammation. There is clinical evidence implicating TREM-1 in the pathogenesis of periodontitis. However, a cause-and-effect relationship has yet to be demonstrated, as is the underlying mechanism. The aim of this study was to elucidate the role of TREM-1 using the murine ligature-induced periodontitis model. Methods: A synthetic antagonistic LP17 peptide or sham control was microinjected locally into the palatal gingiva of the ligated molar teeth. Results: Mice treated with the LP17 inhibitor developed significantly less bone loss as compared to sham-treated mice, although there were no differences in total bacterial load on the ligatures. To elucidate the impact of LP17 on the host response, we analyzed the expression of a number of immune-modulating genes. The LP17 peptide altered the expression of 27/92 genes ≥ two-fold, but only interleukin (IL)-17A was significantly downregulated (4.9-fold). Importantly, LP17 also significantly downregulated the receptor activator of nuclear factor kappa-B-ligand (RANKL) to osteoprotegerin (OPG) ratio that drives osteoclastic bone resorption in periodontitis. Conclusion: Our findings show for the first time that TREM-1 regulates the IL-17A-RANKL/OPG axis and bone loss in experimental periodontitis, and its therapeutic blockade may pave the way to a novel treatment for human periodontitis.
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| 11. |
- Kepp, Kasper P., et al.
(författare)
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Panel stacking is a threat to consensus statement validity
- 2024
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier. - 0895-4356 .- 1878-5921. ; 173
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Tidskriftsartikel (refereegranskat)abstract
- Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.
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