Fant 9888 publikasjoner. Viser side 264 av 396:
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Extracellular Vesicles as Next-Generation Diagnostics and Advanced Therapy Medicinal Products
Extracellular vesicles (EVs) hold great promise for clinical application as new diagnostic and therapeutic modalities. This paper describes major GMP-based upstream and downstream manufacturing processes for EV large-scale production, also focusing on post-processing technologies such as surface bioengineering and uploading studies to yield novel EV-based diagnostics and advanced therapy medicinal products. This paper also focuses on the quality, safety, and efficacy issues of the bioengineered EV drug candidates before first-in-human studies. Because clinical trials involving extracellular vesicles are on the global rise, this paper encompasses different clinical studies registered on clinical-trial register platforms, with varying levels of advancement, highlighting the growing interest in EV-related clinical programs. Navigating the regulatory affairs of EVs poses real challenges, and obtaining marketing authorization for EV-based medicines remains complex due to the lack of specific regulatory guidelines for such novel products. This paper discusses the state-of-the-art regulatory knowledge to date on EV-based diagnostics and medicinal products, highlighting further research and global regulatory needs for the safe and reliable implementation of bioengineered EVs as diagnostic and therapeutic tools in clinical settings. Post-marketing pharmacovigilance for EV-based medicinal products is also presented, mainly addressing such topics as risk assessment and risk management.
MDPI
2024
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ExSIRA - Experimental study to investigate risk of selected amines (project no. 199874/S60). NILU PP
2011
ExSIRA - Experimental study to investigate risk of selected amines (project no. 199874/S60). NILU PP
2013
2012
High levels of organochlorines (OCs) have been measured in arctic char (Salvelinus alpinus) from Lake Ellasjøen on Bjørnøya, Norway (74.30°N, 19.0°E). In a nearby lake, Laksvatn, the OC-levels in arctic char were low. A previous study has shown that char from Ellasjøen had significantly higher levels of DNA double strand breaks (DSBs) than char from Lake Laksvatn. Even though there is increasing evidence of the genotoxic effects of OCs, little is known about the effects of OCs on the DNA repair system. The aim of the present study was to determine if the two main DNA DSB repair mechanisms, homologous recombination (HR) and non-homologous end-joining (NHEJ), are affected by the higher OC and DSB level in char from Ellasjøen. This was analysed by comparing the transcript level of 11 genes involved in DNA DSB repair in char liver samples from Ellasjøen (n = 9) with char from Laksvatn (n = 12). Six of the investigated genes were significantly upregulated in char from Ellasjøen. As the expression of DNA DSB repair genes was increased in the contaminant-exposed char, it is likely that the DNA DSB repair capacity is induced in these individuals. This induction was positively correlated with the DNA DSB and negatively correlated with one or several OCs for four of these genes. However, the strongest predictor variable for DNA repair genes was habitat, indicating genetic differences in repair capacity between populations. As char from Ellasjøen still had significantly higher levels of DSBs compared to char from Laksvatn, it is possible that chronic exposure to OCs and continued production of DSB has caused selective pressure within the population for fixation of adaptive alleles. It is also possible that DSB production was exceeding the repair capacity given the prevailing conditions, or that the OC or DSB level was above the threshold value of inhibition of the DNA repair system resulting in the rate of DNA damage exceeding the rate of repair.
Elsevier
2021
Environmental factors that can influence telomeres are diverse, but the association between telomeres and exposure to environmental contaminants is yet to be elucidated. To date, prior studies have focused on legacy persistent chlorinated pollutants (POPs), while the effects of poly- and perfluoroalkyl substances (PFAS) have been poorly documented. Here, we investigated the associations among PFAS congeners, absolute telomere length (cross-sectional approach), and telomere dynamics (rate of telomere length change over time, longitudinal approach) in one of the most contaminated arctic top predators, the glaucous gull Larus hyperboreus from Svalbard. We further estimated the effect of PFAS on apparent survival rates and re-sighting probabilities using a 10-year capture/recapture dataset (2010–2019). We found that birds exposed to higher concentrations of perfluorononadecanoate (PFNA) (median of 1565 pg/mL of ww in males and 1370 pg/mL of ww in females) and perfluorotetradecanoate (PFTeDA) (median of 370 pg/mL of ww in males and 210 pg/mL of ww in females) showed the slowest rate of telomere shortening. We also found that high blood concentrations of perfluorooctanoate (PFOA) (median of 120 pg/mL of ww in males and 150 pg/mL of ww in females) and perfluorohexanesulfonate (PFHxS) (median of 495 pg/mL of ww in males and 395 pg/mL of ww in females) were positively associated with higher re-sighting probabilities and apparent survival in males but not in females. Our work is the first to report an association between single PFAS compounds and telomeres, and the first to link PFAS exposure with survival probabilities, suggesting that the effect of PFAS exposure might be more tied to the type of compound rather than the total concentration of PFAS.
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