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- Kent, Robyn S, et al.
(författare)
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Inducible developmental reprogramming redefines commitment to sexual development in the malaria parasite Plasmodium berghei
- 2018
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Ingår i: Nature Microbiology. - : Nature Publishing Group. - 2058-5276. ; 3:11, s. 1206-1213
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Tidskriftsartikel (refereegranskat)abstract
- During malaria infection, Plasmodium spp. parasites cyclically invade red blood cells and can follow two different developmental pathways. They can either replicate asexually to sustain the infection, or differentiate into gametocytes, the sexual stage that can be taken up by mosquitoes, ultimately leading to disease transmission. Despite its importance for malaria control, the process of gametocytogenesis remains poorly understood, partially due to the difficulty of generating high numbers of sexually committed parasites in laboratory conditions1. Recently, an apicomplexa-specific transcription factor (AP2-G) was identified as necessary for gametocyte production in multiple Plasmodium species2,3, and suggested to be an epigenetically regulated master switch that initiates gametocytogenesis4,5. Here we show that in a rodent malaria parasite, Plasmodium berghei, conditional overexpression of AP2-G can be used to synchronously convert the great majority of the population into fertile gametocytes. This discovery allowed us to redefine the time frame of sexual commitment, identify a number of putative AP2-G targets and chart the sequence of transcriptional changes through gametocyte development, including the observation that gender-specific transcription occurred within 6 h of induction. These data provide entry points for further detailed characterization of the key process required for malaria transmission.
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| 3. |
- Mehta, Meenu, et al.
(författare)
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Recent trends of NFkB decoy oligodeoxynucleotide-based nanotherapeutics in lung diseases
- 2021
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Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 337, s. 629-644
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Forskningsöversikt (refereegranskat)abstract
- Nuclear factor Kappa B (NFicB) is a unique protein complex that plays a major role in lung inflammation and respi-ratory dysfunction. The NFicB signaling pathway, therefore becomes an avenue for the development of potential pharmacological interventions, especially in situations where chronic inflammation is often constitutively active and plays a key role in the pathogenesis and progression of the disease. NFicB decoy oligodeoxynucleotides (ODNs) are double-stranded and carry NFicB binding sequences. They prevent the formation of NFicB-mediated inflammatory cytokines and thus have been employed in the treatment of a variety of chronic inflammatory diseases. However, the systemic administration of naked decoy ODNs restricts their therapeutic effectiveness because of their poor pharmacokinetic profile, instability, degradation by cellular enzymes and their low cellular uptake. Both structural modification and nanotechnology have shown promising results in enhancing the pharmacokinetic profiles of potent therapeutic substances and have also shown great potential in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. In this review, we examine the contribution of NFicB activation in respiratory diseases and recent advancements in the thera-peutic use of decoy ODNs. In addition, we also highlight the limitations and challenges in use of decoy ODNs as therapeutic molecules, cellular uptake of decoy ODNs, and the current need for novel delivery systems to provide efficient delivery of decoy ODNs. Furthermore, this review provides a common platform for discussion on the existence of decoy ODNs, as well as outlining perspectives on the latest generation of delivery systems that encapsulate decoy ODNs and target NFxB in respiratory diseases.
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- Paudel, Keshav Raj, et al.
(författare)
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Recent Advances in Chronotherapy Targeting Respiratory Diseases
- 2021
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923 .- 1999-4923. ; 13:12
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Forskningsöversikt (refereegranskat)abstract
- Respiratory diseases contribute to a significant percentage of mortality and morbidity worldwide. The circadian rhythm is a natural biological process where our bodily functions align with the 24 h oscillation (sleep-wake cycle) process and are controlled by the circadian clock protein/gene. Disruption of the circadian rhythm could alter normal lung function. Chronotherapy is a type of therapy provided at specific time intervals based on an individual's circadian rhythm. This would allow the drug to show optimum action, and thereby modulate its pharmacokinetics to lessen unwanted or unintended effects. In this review, we deliberated on the recent advances employed in chrono-targeted therapeutics for chronic respiratory diseases.
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