Purpose: This study aimed to develop a hyperosmolar, barrier-forming nasal spray based on carrageenan and sorbitol, and to demonstrate its decongestant effect in the context of allergic rhinitis (AR).
Methods: The efficacy of the nasal spray components was tested in vitro by barrier function, virus replication inhibition, and water absorption assays. The decongestant effectiveness was assessed in a randomized, controlled, crossover environmental chamber trial, where participants with a history of seasonal grass pollen AR were exposed to grass pollen allergens under controlled conditions.
Purpose: This randomized, placebo-controlled, crossover, double-blind trial aimed to evaluate the efficacy and safety of Tacrosolv, a novel 0.005% tacrolimus eye-drop solution, in adults with grass pollen-induced allergic conjunctivitis.
Methods: A total of 64 adult participants were randomized to receive 2.
Objectives: Booster doses for COVID-19 vaccinations have been shown to amplify the waning immune response after primary vaccination and to enhance protection against emerging variants of concern (VoCs). Here, we aimed to assess the immunogenicity and safety of a booster dose of an inactivated whole-virus COVID-19 vaccine (VLA2001) after primary vaccination with 2 doses of either VLA2001 or ChAdOx1-S (Oxford-Astra Zeneca), including the cross-neutralization capacity against the Delta and Omicron VoCs.
Methods: This interim analysis of an open-label extension of a randomized, controlled phase 3 trial assessed a single booster dose of an inactivated whole-virus COVID-19 vaccine (VLA2001) in healthy or medically stable adults aged 18 years and above, recruited in 21 clinical sites in the UK, who had previously received two doses of either VLA2001 or ChAdOx1-S.
The mechanisms by which protein complexes convert from functional to pathogenic are the subject of intensive research. Here, we report how functionally unfavorable protein interactions can be induced by structural fuzziness, i.e.
View Article and Find Full Text PDFLoss of functionality during aging of cells and organisms is caused and accompanied by altered cell-to-cell communication and signalling. One factor thereby is the chronic accumulation of senescent cells and the concomitant senescence-associated secretory phenotype (SASP) that contributes to microenvironment remodelling and a pro-inflammatory status. While protein based SASP factors have been well characterized, little is known about small extracellular vesicles (sEVs) and their miRNA cargo.
View Article and Find Full Text PDFThere is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life- and healthspan of mice. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). Here we identified an extract from the plant subsp.
View Article and Find Full Text PDFBackground: Osteoporosis poses an immense burden to the society in terms of morbidity, mortality and financial cost. To reduce this burden, it is essential to accurately assess the individual patient's fracture risk and, where indicated, to initiate appropriate treatment that reduces fracture probability. Current screening and monitoring approaches include utilization of FRAX®, a web-based country-specific fracture risk assessment tool, and bone mineral density measurement by Dual Energy X-ray Absorptiometry (DXA).
View Article and Find Full Text PDFSoon after microRNAs entered the stage as novel regulators of gene expression, they were found to regulate -and to be regulated by- the development, progression and aggressiveness of virtually all human types of cancer. Therefore, miRNAs in general harbor a huge potential as diagnostic and prognostic markers as well as potential therapeutic targets in cancer. The miR-17-92 cluster was found to be overexpressed in many human cancers and to promote unrestrained cell growth, and has therefore been termed onco-miR-1.
View Article and Find Full Text PDFMechanisms that ensure and maintain the stability of genetic information are fundamentally important for organismal function and can have a large impact on disease, aging, and life span. While a multi-layered cellular apparatus exists to detect and respond to DNA damage, various insults from environmental and endogenous sources continuously affect DNA integrity. Over time this can lead to the accumulation of somatic mutations, which is thought to be one of the major causes of aging.
View Article and Find Full Text PDFAging is accompanied by loss of subcutaneous adipose tissue. This may be due to reduced differentiation capacity or deficiency in DNA damage repair (DDR) factors. Here we investigated the role of SNEV, which was implicated in DDR and senescence evasion, in adipogenic differentiation of human adipose stromal cells (hASCs).
View Article and Find Full Text PDFThe miR-17-92 cluster, led by its most prominent member, miR-17-5p, has been identified as the first miRNA with oncogenic potential. Thus, the whole cluster containing miR-17-5p has been termed oncomiR-1. It is strongly expressed in embryonic stem cells and has essential roles in vital processes like cell cycle regulation, proliferation and apoptosis.
View Article and Find Full Text PDFSenescent cells accumulate during ageing in various tissues and contribute to organismal ageing. However, factors that are involved in the induction of senescence in vivo are still not well understood. SNEV(P) (rp19/) (PSO) (4) is a multifaceted protein, known to be involved in DNA damage repair and senescence, albeit only in vitro.
View Article and Find Full Text PDFSeveral pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is unclear. Here, we show that reduced levels of the conserved RNA methyltransferase NSUN5 increase the lifespan and stress resistance in yeast, worms and flies. Rcm1, the yeast homologue of NSUN5, methylates C2278 within a conserved region of 25S rRNA.
View Article and Find Full Text PDFCellular senescence of normal human cells has by now far exceeded its initial role as a model system for aging research. Many reports show the accumulation of senescent cells in vivo, their effect on their microenvironment and its double-edged role as tumour suppressor and promoter. Importantly, removal of senescent cells delays the onset of age-associated diseases in mouse model systems.
View Article and Find Full Text PDFDefective DNA repair is widely acknowledged to negatively impact on healthy aging, since mutations in DNA repair factors lead to accelerated and premature aging. However, the opposite, namely if improved DNA repair will also increase the life or health span is less clear, and only few studies have tested if overexpression of DNA repair factors modulates life and health span in cells or organisms. Recently, we identified and characterized SNEVhPrp19/hPso4, a protein that plays a role in DNA repair and pre-mRNA splicing, and observed a doubling of the replicative life span upon ectopic overexpression, accompanied by lower basal DNA damage and apoptosis levels as well as an increased resistance to oxidative stress.
View Article and Find Full Text PDFThe Cdc5L (cell division cycle 5-like) complex is a spliceosomal subcomplex that also plays a role in DNA repair. The complex contains the splicing factor hPrp19, also known as SNEV or hPso4, which is involved in cellular life-span regulation and proteasomal breakdown. In a recent large-scale proteomics analysis for proteins associated with this complex, proteins involved in transcription, cell-cycle regulation, DNA repair, the ubiquitin-proteasome system, chromatin remodelling, cellular aging, the cytoskeleton and trafficking, including four members of the exocyst complex, were identified.
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